Endocrine Flashcards
What does the anterior pituitary gland produce?
Growth Hormone Adenocortico-tropic Hormone Follicle Stimulating Hormone Luteinizing Hormone Prolactin TSH Melanocyte Stimulating Hormone
What does the posterior pituitary gland produce?
ADH (vasopressin)
Oxytocin
HPA Axis includes?
Hypothalamus
Anterior Pituitary
Adrenal Cortex
Types of pituitary neoplasms?
Adenomas
Carcinomas (v rare)
Mets (breast, lung, GIT)
Features of pituitary adenomas?
most are small/incidental
functioning: effects vary
non-functioning: pressure effects, hypopituitarism
Most common cause of hyperpituitarism?
Pituitary adenoma
Most common pituitary adenomas?
Prolactinomas
GH adenomas
ACTH cell adenomas
Who are prolactinomas most frequently diagnosed in?
most commonly in menstruating women- their period stops
What is the most common pituitary adenoma?
Prolactinoma
Symptoms of GH adenomas?
Inc. growth- bone and soft tissue
‘sausage digits’
ACTH adenoma causes what?
Cushing’s Disease
Causes of hypopituitarism?
surgery
irradiation
apoplexy/ischaemia
pressure effects of neoplasm
Diagnosis of hypopituitarism?
low serum corticosteroid levels
normal response to ACTH
Deficiency of ADH causes?
Diabetes Insipidus
Excess of ADH causes?
SIADH
Most common cause of goitre?
Dietary iodine deficiency
2 types of goitre are?
Diffuse (non-toxic) simple goitre
Multi-nodular goitre
Abrupt enlargement of goitre most likely cause?
Haemorrhage
Symptoms of hyperthyroidism?
palpitations, weight loss, inc. appetite, nervousness, sweating, heat intolerance, diarrhoea, arrhythmias, osteoporosis, exophthalmos (Grave’s)
Hyperthyroidism presentation in bloods?
Elevated T3, T4
Low TSH
Causes of hyperthyroidism?
Grave’s Disease
Multi-Nodular Goitre with toxic nodule
Toxic adenoma
Most common cause of hyperthyroidism?
Grave’s Disease (85%)
Grave’s Disease symptoms?
Hyperthyroidism
Exophthalmos
Pretibial myxoedema
Grave’s Disease mechanism?
Anti TSH receptor antibodies
Histological appearance of Grave’s Disease?
hyperplasia hypertrophy papillary infoldings scalloping of colloid lymphoid infiltrate
Causes of hypothyroidism?
Autoimmune- Hashimoto’s Disease
Post-ablative- surgery, radiation, radioactive iodine
Others- severe iodine deficiency, metabolism errors, drugs
Symptoms of hypothyroidism?
tiredness, cold intolerance, mental and physical slowing, weight gain, constipation, depression, muscle aches, dry and scaly skin, brittle nails and hair, cretinism
Hypothyroidism on blood tests?
Low T3, T4
High TSH
Hashimoto’s Thyroiditis presentation?
Painless Diffuse enlarged gland (early)
Shrunken fibrosed gland (late)
Histology of Hashimoto’s?
lymphocytic infiltrate with germinal centres
hurthle cell change
fibrosis
What appears as a hot nodule on radioactive iodine scan?
toxic adenoma
toxic nodule in MNG
What appears as a cold nodule on radioactive iodine scan?
neoplasms
cysts
What appears as a diffuse increased uptake?
Grave’s Disease
What appears as a diffuse decreased uptake?
Thyroiditis
How does a MNG appear on radioactive iodine scan?
Patchy, irregular uptake
Neoplasms of the thyroid?
Adenomas- follicular
Carcinomas- follicular, papillary, medullary, anaplastic
Others- lymphoma, mets
What percentage of follicular adenomas are toxic?
1%
Presentation of follicular adenoma?
Encapsulated follicular lesion
Reasons to favour follicular adenoma as a diagnosis rather than adenomatoid nodule?
single completely encapsulated dissimilar to adjacent thyroid composed of follicles smaller than adjacent thyroid compresses adjacent tissue
What differentiates follicular adenoma from follicular carcinoma?
No capsular or vascular invasion in follicular adenoma
Follicular Carcinoma features?
follicular pattern looks like follicular adenoma vascular invasion capsular invasion mets
Spread of follicular carcinoma?
doesn’t usually spread to LNs
liver, lung, brain, bone
Treatment of follicular carcinoma?
Surgery, Iodine 131, thyroxine
Papillary Carcinoma features?
Presents from 20yrs onwards
LN mets early
blood spread uncommon and late
good prognosis
Papillary carcinoma histologically?
papillary or follicular pattern
nuclear features key to diagnosis
Treatment of papillary carcinoma?
Surgery, Iodine 131, thyroxine
Nuclear features of papillary carcinoma?
enlargement overlapping grooves nuclear inclusions smooth chromatin pattern 'Orphan Annie' nuclei Psammoma bodies/calcifications
What percentage of thyroid malignancies are medullary carcinomas?
5-10%
What cells do medullary carcinomas evolve from?
neuroendocrine C cells
What is elevated in medullary carcinomas?
Calcitonin
What does elevated calcitonin indicate?
Medullary Carcinoma
Causes of medullary carcinoma?
80% sporadic
MEN 2A or 2B
Familial medullary carcinoma
Outcome of thyroid cancers?
Papillary carcinoma- fatality 5%
Follicular carcinoma- fatality 20%
Medullary carcinoma- fatality 50%
What percentage of thyroid malignancies are anaplastic?
5-10%
Prognosis for anaplastic carcinoma?
Dismal, mortality >95%
Mutations involved in thyroid malignancies?
BRAF
RAS
RET/PTC
PAX8/PPAR
Does RAS mutation distinguish between benign and malignant?
No
20% of follicular adenomas have RAS mutation
40% of follicular carcinomas have it too
What does PTH do?
Increases blood calcium levels
How does PTH increase blood calcium levels?
increase resorption of bone increase Ca absorption from GIT increase Ca reabsorption from kidneys increase urinary excretion of PO4 enhances action of Vit D
What happens if blood calcium level is too high?
Thyroid releases calcitonin
What happens if blood calcium level is too low?
Parathyroid releases PTH
Primary causes of hyperparathyroidism?
Adenoma (80%)
Hyperplasia
Carcinoma (rare)
Secondary causes of hyperparathyroidism?
CKD
response to hypocalcaemia
Tertiary cause of hyperparathyroidism?
Autonomous production of PTH
How do primary, secondary and tertiary hyperparathyroidism present?
Primary- elevated Ca and PTH
Secondary- normal Ca, elevated PTH
Tertiary- elevated Ca and PTH
Symptoms of primary hyperparathyroidism?
Bones, stones, groans and moans
How to distinguish between adenoma and hyperplasia?
Adenoma- normal gland, compressed rim of parathyroid gland at the periphery
What causes T1DM?
autoimmune destruction of the beta cells in the islets of langerhan in the pancreas
What HLAs are associated with T1DM?
HLA-DR3 and HLA-DR4
Clinical features of T1DM?
young patient thin polydipsia polyuria visual blurring dehydration DKA
2 key components to T2DM?
reduced ability of tissues to respond to insulin (obesity)
beta cell dysfunction (initially qualitative, followed by quantitative)
Clinical features of T2DM?
middle-aged high BMI sedentary lifestyle HTN Hypercholesterolaemia may be asymptomatic (GP screening) may present with advanced complications
Complications of DM?
Macrovascular Microvascular DKA HONK Hypoglycaemia
Macrovascular complications of DM?
atherosclerosis
MI
stroke
peripheral vascular disease
Microvascular complications of DM?
Diabetic retinopathy
Diabetic nephropathy
Diabetic neuropathy
Features of diabetic retinopathy?
thickening of BM leaky capillaries oedema microhaemorrhages exudate
Two types of DR?
Non-proliferative (early)
Proliferative (later, angiogenesis)
3 main lesions in diabetic nephropathy?
Glomerular lesions
Renal vascular lesions
Pyelonephritis
What type of glomerular lesion is seen in DNephropathy?
nodular glomerulosclerosis/Kimmelsteil-Wilson lesions
What is seen in renal vascular lesions due to diabetes?
hyaline arteriosclerosis
What is seen in diabetic pyelonephritis?
Papillary necrosis
What causes diabetic neuropathy?
toxic effects on neurons due to oxidative stress related to hyperglycaemia
3 types of Diabetic Neuropathy?
Diffuse- Distal symmetrical sensorimotor polyneuropathy
Focal- mononeuropathy (cranial)
Diabetic autonomic neuropathy
What causes HONK?
decrease in extracellular fluid level, may be precipitated by infection, dehydration etc.
Treatment of HONK?
Fluid resuscitation with K and insulin
Risk factors for hypoglycaemia?
Tight glucose control Alcohol Insulin prescription error Long history of diabetes renal dialysis malabsorption drugs lack of anti-insulin hormone function (Addison's, hypothyroidism)
Hypoglycaemia treatment?
If conscious, oral glucose
If unconscious, IV glucose
What does the adrenal cortex produce?
aldosterone, cortisol, sex hormones
What does the adrenal medulla produce?
catecholamines (adrenaline, noradrenaline)
What is Addison’s disease?
primary adrenal insufficiency
When does Addison’s disease become symptomatic?
When >90% of the cortex has been destroyed
Presentation of Addison’s disease?
insidious onset progressive weakness, fatigue GI disturbances hyperpigmentation Hyperkalaemia, hyponatremia, volume depletion hypotension
Pathology of Addison’s Disease?
adrenal gland is shrunken in autoimmune disease
adrenal gland is enlarged in infection, mets
How does acute adrenal insufficiency present?
intractable vomiting, abdominal pain, hypotension, coma, vascular collapse
Treatment of acute adrenal insufficiency?
Steroid ASAP
or else death
What causes secondary hypoadrenalism?
any cause if hypothalamic or pituitary loss of function
What distinguishes primary from secondary hypoadrenalism?
no hyperpigmentation in secondary
normal aldosterone synthesis-> K and Na are normal
low levels of both ACTH and cortisol
rise is seen in cortisol levels after exogenous ACTH given
What causes Cushing’s syndrome?
cortisol excess
Symptoms of Cushing’s syndrome?
moon facies buffalo hump hirsutism easy bruising HTN proximal muscle weakness menstrual abnormalities DM osteoporosis
Most common cause of Cushing’s syndrome?
Exogenous steroids
Endogenous causes of Cushing’s syndrome?
pituitary adenoma (Cushing’s disease)
cortisol hypersecretion due to adrenal tumour or hyperplasia
ectopic ACTH secretion due to neoplasm e.g., lung
Diagnosis of Cushing’s Syndrome?
increased free cortisol in urine
lack of diurnal rhythm
failure to suppress cortisol (low dexamethasone suppression test, high dexamethasone suppression test)
Results of dexamethasone suppression test?
pituitary adenoma (initial serum levels of ACTH- high, urine steroids following high dose dex.- suppressed) ectopic ACTH (initial serum levels of ACTH- v high, not suppressed) adrenocortical neoplasm (initial serum levels of ACTH- v low, not suppressed)
Adrenal appearance in Cushing’s syndrome?
cortical atrophy (exogenous steroids) diffuse or nodular hyperplasia (endogenous causes) mass present (adenoma or carcinoma)
Main cause of primary hyperaldosteronism?
cortical adenoma (>90% are Conn’s syndrome)
What is Conn’s syndrome?
primary hyperaldosteronism
most often caused by adrenal adenoma
Features of Conn’s syndrome?
Low K
Inc. Na
Oedema
HTN
Causes of secondary hyperaldosteronism?
activation of RAS
renal artery stenosis
arterial hypovolemia/oedema
Causes of adrenogenital syndromes?
Excess production of adrenal androgens:
adrenocortical neoplasms
congenital adrenal hyperplasia
bilateral nodular hyperplasia (e.g., Cushings)
What causes congenital adrenal hyperplasia?
21 hydroxylase deficiency
Adrenal neoplasms?
Cortex- adenoma, carcinoma
Medulla- neuroblastoma, pheochromocytoma
What score is used to differentiate between adenoma and carcinoma?
WEISS score
>3 indicates carcinoma
WEISS score criteria?
mitotic activity atypical mitoses nuclear pleomorphism absence of clear cells diffuse architecture necrosis capsular invasion venous invasion sinusoidal invasion
When do the majority of neuroblastomas occur?
<5 years of age
Prognosis of neuroblastoma is related to?
Age (younger=better)
Stage
Histological features
Genetic factors
What genetic factors indicate a poorer prognosis for neuroblastomas?
N-Myc gene amplification
Chr 17q gain, 1p loss
How does a neuroblastoma present?
small round blue cell tumour
neurosecretory granules
What do pheochromocytomas produce?
Catecholamines
Presentation of pheochromocytomas?
HTN, palpitations, flushing
Diagnosis of pheochromocytomas?
Elevated serum catecholamine
Elevated urine catecholamines and VMA
What percentage of pheochromocytomas are malignant?
10%
What percentage of pheochromocytomas are familial related and what conditions are involved?
10% MEN 2a and 2b Von Hippau Lindel syndrome neurofibromatosis sturge weber familial SDH mutations
What is Sheehan Syndrome?
maternal hypopituitarism caused by excessive blood loss during or after the delivery of a baby
What bone condition is associated with hyperparathyroidism?
Osteo fibrosa cystica
