Endocrinology Flashcards
What are the 4 hormones involved in appetite regulation?
What do each of them do and detect?
INCREASE SATIETY AND REDUCE APPETITE
Leptin - detects lipids
Insulin - detects carbohydrates
REDUCE SATIETY AND INCREASES APPETITE
Ghrelin and GLP-1 (glucagon-like peptide 1)
Difference between Cushing’s syndrome and Cushing’s disease
Cushing’s syndrome: general term for chronic excessive and inappropriate elevated levels of circulating CORTISOL
Cushing’s disease: excessive cortisol resulting from inappropriate ACTH secretion due to pituitary tumour
CUSHING'S BACKGROUND What releases CRH? Full name? What releases ACTH? Full name? What releases cortisol? Proportion in blood? Bound to? Effects of cortisol (6)
Hypothalamus releases corticotrophin releasing hormone.
Pituitary gland releases adenocorticotrophic hormone.
Zona fasiculata releases cortisol.
95% cortisol binding globulin, 5% free
Increased gluconeogenesis, proteolysis, lipolysis. Increased BP. Anti-inflammatory. Mood and memory.
CUSHING’S SIGNS AND SYMPTOMS
Big 3?
Others?
MOON FACE, OBESITY, BUFFALO HUMP
Mood changes, infection?, thin skin, bruises, osteoporosis, purple striae, acne, increased BP
CUSHING’S DIFFERENTIAL DIAGNOSIS?
Pseudo-Cushing’s syndrome
Caused by alcohol excess - resolves with abstinence
CUSHING’S DIAGNOSIS?
Initial?
First line?
2nd line?
Initial - urine, blood, saliva cortisol
First line - dexamethasone suppression test
(overnight or 48hr)
Second line - ACTH test and dexamethasone injected
ACTH high - pituitary or ectopic
ACTH low - adrenal tumours
CT and MRIs to confirm
CUSHING’S CAUSES?
Exogenous - oral steroids (most common)
Endogenous -
ACTH dependent: pituitary or ectopic
ACTH independent: adrenal tumour
CUSHING’S TREATMENT?
Stops steroids
Surgery on tumours
Medications: inhibit cortisol synthesis, eg METYRAPONE, KETOCONAZOLE, FLUCONAZOLE
ACROMEGALY vs GIGANTISM?
Acromegaly - hormone disorder in adults as a result of excess growth hormone
Gigantism - excess growth hormone in childhood, leading to increased height
ACROMEGALY BACKGROUND
Feedback mechanisms on GH?
Two groupings for GH effects? Examples?
GHRH from hypothalamus stimulates
Somatostatin from muscle, liver, bones inhibits
Direct: increased metabolism and growth increased bone thickness and muscle growth increased insulin resistance increased glucose in blood
Indirect: via IGF-1
increased metabolism, increased cell division and differentiation, prevents cell death
ACROMEGALY EPIDEMIOLOGY AND RISK FACTORS How common? Male vs Female? Age? Specific risk factor
Rare - 3 per million in the UK
Male = Female
Middle age
MEN-1 (multiple endocrine neoplasia)
ACROMEGALY CAUSES
Main?
3 others?
99% of cases: functional pituitary adenoma
also:
ectopic, hypothalamic tumour, MEN-1
ACROMEGALY SIGNS AND SYMPTOMS
List as many as possible.
Note on diagnosis?
Often takes years to diagnose
Headaches increased size of extremities sweating snoring decreased libido amenorrhea skin darkens wide nose deep voice macroglossia
ACROMEGALY COMPLICATIONS
5 examples
Impaired glucose tolerance (40%) Leading to diabetes mellitus (15%) Carpal tunnel syndrome HTN, cardiac problems Colon cancer
ACROMEGALY DIAGNOSIS
3 steps
Test for increased IGF-1 (diagnostic) and GH (non-diagnostic)
Oral glucose tolerance test (OGTT) - glucose should suppress GH
MRI for pituitary adenoma
ACROMEGALY TREATMENT
1st line?
2nd line?
3rd line?
1: Trans-sphenoidal surgery (+radiotherapy?)
2: Somatostatin analogues, eg octreotide or lanreotide
3: GH antagonist (pregvisomant)
ADRENAL INSUFFICIENCY CAUSES
2 categories? Examples?
Primary (ADDISON’S DISEASE)
autoimmune (80%)
TB, metastatic carcinoma, lymphoma, CMV in HIV, adrenal haemorrhage
Secondary
long term steroid use
hypothalamic-pituitary disease (ACTH)
ADRENAL INSUFFICIENCY EPIDEMIOLOGY
How common?
Can it be fatal? Expand on this
Rare - 0.3 per 100,000
Can be fatal - ADDISONIAN CRISIS
untreated w/ bad destruction, leads to dehydration, low BP, tachycardia: possibly death
ADRENAL INSUFFICIENCY SIGNS AND SYMPTOMS?
Split up into 3 categories
- Due to lack of aldosterone
hyperkalaemia, hyponatraemia, hypovolemia, metabolic acidosis, craving salts, NAUSEA, fatigue - Due to lack of cortisol
glucose down, weakness, tiredness, BRONZE PIGMENTATION - Due to lack of androgens
women only: decreased libido and changes/decreases in body hair
ADRENAL INSUFFICIENCY DIAGNOSIS & TREATMENT
First line?
Second line?
1st Blood tests:
sodium, potassium, hormones, etc
2nd ACTH stimulation test:
synthetic ACTH given, measure the cortisol and aldosterone, should increase if healthy
Treatment: Replace hormones
HYDROCORTISONE/PREDNISOLONE (gluco-)
FLUDROCORTISONE (mineral-)
HYPERALDOSTERONISM BACKGROUND
What are the actions of aldosterone? On what cells?
Use these to show signs of hyperaldosteronism.
Principle cell (Na+ and H20 in, K+ out) Hypernatermia, Hypervolemia, Hypokalaemia
Alpha Intercalated Cell (H+ excretion)
Metabolic alkalosis
HYPERALDOSTERONISM EPIDEMIOLOGY AND RISK FACTORS
What is HYPERALDOSTERONISM a rare cause of? How much?
When to check for HYPERALDOSTERONISM?
Rare cause of HTN (less than 1%)
Check for patients with HTN under 35 with no family history
HYPERALDOSTERONISM CAUSES
2 categories?
2 (w/ numbers) x 2
Primary (pathology with adrenal gland)
- adrenal adenoma (CONN’S SYNDROME) (2/3)
- idiopathic bilateral hyperplasia (1/3)
Secondary (pathology elsewhere, increased Renin)
- chronic low BP (heart failure)
- reduced renal perfusion
HYPERALDOSTERONISM CLINICAL FEATURES?
Often?
5.
OFTEN ASYMPTOMATIC
Hypertension, Muscle weakness and paraesthesiae
Polydipsia, polyuria
HYPERALDOSTERONISM DIAGNOSIS
1st tests
2nd tests
Blood tests: U and Es, Aldo, Renin (ARR)
ECG: (hypokalaemia)
24hr aldosterone test (confirmatory)
Adrenal CT scan
HYPERALDOSTERONISM TREATMENT
Main principle:
3 leads from this principle.
Specific medication?
= Treat the cause
- Conn’s (surgery)
- Bilateral Hyperplasia (medication - oral spironolactone, potassium sparing diuretic)
- Heart Failure (normal treatment)
How are pituitary tumours categorised?
3 ways with examples
Size
- microadenoma <1cm, macroadenoma >1cm
Functional (less common - prolactinioma, Cushing’s disease, main cause of Acromegaly)
Non-functional (more common)
Histology
Chromophobe
Acidophil - somatotrophs, lactrotrophs
Basophil - corticotroph, thyrotrophs
3 key signs of a large pituitary tumour
Bilateral temporal hemianopia - starts at top
Palsy of cranial nerves III, IV, VI (eye movement)
CSF rhinorrhoea
What is a pituitary apoplexy?
When do it occur?
A rapid pituitary enlargement due to bleeding into the tumour
Very serious - needs urgent treatment
Can occur as a complication of a pituitary tumour
What is a prolactinoma?
Symptoms? - M vs W
How is it treated? Main example and other
Functional adenoma of lactotrophs that secrete prolactin.
W: Amenorrhea and galactorrhea
M: Low libido and gynecomastia
Treated with BROMOCRIPTINE (main) or CABERGOLINE (dopamine agonists)
Treated with surgery if macroadenoma
What is a craniopharngioma?
Mostly occurs in?
Symptoms?
Tumour orgininates from Rathke’s pouch
Most commonly occurs in children - causes hypopituitarism symptoms and pituitary gland tumour symptoms
What is a neuroblastoma? Who does it occur in? Symptoms? 3 types? Dx and Management?
Tumour of neuroblasts - don’t differentiate properly when forming the adrenal medulla
Usually in infants (less than 5 years old)
Fever, weight loss, sweating, BRUISING AROUND EYES
Differentiated, undifferentiated, poorly differentiated.
CT scan, adrenaline and noradrenaline metabolites (HMA and VMA)
Surgery, chemotherapy, stem cell or bone marrow transplant
What is a pheochromocytoma?
What is the base cell?
Symptoms?
Dx and management?
Rare adrenal gland tumour in the medulla - characterised by the darkening of cells
Chromaffin cells
PHEochromocytoma:
palpitations, headaches, episodic sweating
Test for catecholamines in blood
Surgery
Causes for thyroid nodules?
Multinodular goitre Benign follicular adenoma Thyroid cysts (95% - benign) Thyroid cancers (5%)
Types of thyroid cancers?
Which are the most common?
Which are the most aggressive?
Who do they normally occur in?
DIFFERENTIATED:
papillary (70%) - from follicular cells, young
follicular (20%) - from follicular cells, middle age
medullary (5%) - from calcitonin C cells
Anaplastic - (>5%) from follicular, aggressive, poor prognosis
Clinical presentation in thyroid tumours
Solitary, painless nodule (hard and immovable)
Later: dysphagia or hoarseness of voice from tumour, goitre?
How to diagnose thyroid tumours? 4 possible tests
Fine needle aspiration
Blood tests - TSH, T4, T3, calcitonin
Radioiodine scan (normally cold)
Thyroid ultrascan
How to treat thyroid cancers?
Thyroidectomy (partial or full)
Thyroid Hormone Replacement (TSH is a growth factor to cancer: will keep it down)
Chemotherapy
What is goitre? Two types and causes of these types?
= enlarged thyroid gland
Diffuse = physiological, Grave's, Hasimoto's Nodular = multinodular, adenoma, cyst, carcinoma
Prevalence of hypothyroidism vs hyperthyroidism
HYPER = 2,5% HYPO = 5%
Summary of Grave’s disease pathophysiology?
Antibody?
Autoimmune disease inducing excess production of thyroid hormone
Main: TSH Receptor antibody (TSHR-Ab)
GRAVE'S DISEASE EPIDEMIOLOGY AND RISK FACTORS Fraction cause of hyperthyroid? Females vs Males? Age? Other risk factors?
2/3 cause of HYPERTHYROID
Females»_space; Male (9:1)
40-60 years old
Genetics, stress, smoking, other AI diseases
GRAVE’S DIAGNOSTIC TRIAD?
Hyperthyroidism: weight loss, despite appetite, goitre, heat intolerance, increased heart rate, sweating, anxiety, thin hair
Grave’s opthalmopathy:
inflammation and sweating of eyes, lid lag, exopthalmos
Grave’s dermopathy:
Pretibial myxoedema - waxy, orange, swelling on anterior of feet
MAJOR COMPLICATION OF HYPERTHYROIDISM?
Name?
Symptoms?
Thyroid storm - needs immediate treatment
Heat intolerance into HIGH FEVER
Tachycardia into CARDIAC ARRHYTHMIA
DIAGNOSTIC TESTS FOR THYROID DISORDERS?
Measure TSH, T3, T4
Antibodies (TPO-Ab, TSHR-Ab, Tg-Ab)
Radioiodine scans
FBC for anaemia?
4 POSSIBLE MANAGEMENT STRATEGIES FOR GRAVE’S?
Beta-blockers (propanolol)
Anti-thyroid drugs (carbimazole)
Radio-iodine therapy
Thyroidectomy
Causes of hyperthyroidism? As many as possible
Grave’s (main), toxic multinodular goitre, functional thyroid adenoma, thyroiditis, Jod-Basedow (iodine intake), drugs (amiodarone), neonatal, ectopic
TSH pituitary tumour
Hyperthyroidism symptoms? As many as possible
Weight loss, heat intolerance, fast HR, sweating, anxiety, insomnia, tremor, irritance, diarrhoea, menstrual changes, thin hair, Grave’s specific pathologies
What is Hashimoto’s thyroiditis?
Antigens?
Thyroid gland is attacked by immune system?
TPO-Ab (thyroid peroxidase antibody)
TgAb (thyroglobulin antibody)
HASHIMOTO’S THYROIDITIS: symptoms, and risk factors, management?
Early: often asymptomatic
Later: intial goitre, later shrinkage, goitre
Women»_space; Men (7:1), other AI diseases, family history
Levothyroxine treatment (thyroid replacement)
Causes of hypothyroidism? As many as possible
Iodine deficiency, Hashimoto’s thyroiditis, atrophy, surgery, drug-induced (anti-thyroid, amiodarone)
Tumour of anterior pituitary, hypothalamic damage
Hypothyroidism symptoms? As many as possible
BRADYCARDIC (signs)
Weight gain, cold sensitivity, decreased HR, mental slowness, tiredness, lethargy, low mood, constipation B Reflexes Ataxia Dry skin Yawning/Tiredness Cold sensitivity Ascites Round face/weight gain Depression Immobile Cystic fibrosis
MAJOR COMPLICATION OF HYPOTHYROIDISM?
Symptoms?
MYXOEDEMA COMA (severe)
Exaggerated hypothyroidism symptoms:
mental slowness, hypothermia, confusion
siADH BACKGROUND Other name for ADH? What receptor does ADH bind to? What does it cause in the kidney? What triggers release? Biggest cause of what?
Vasopessin
V2 receptor
Causes aquaporin 2 channels to merge with membrane, causing increased water retention in blood
Triggered by high osmolarity or decrease in blood volume
25% cause of hyponatraemia
siADH AETIOLOGY
List some causes? Categories
Ectopic tumours - release ADH
CNS - strokes, meningitis, trauma
Pulmonary lesions
Hypothyroidism, alcohol withdrawel, drugs
siADH SIGNS AND SYMPTOMS
Mild and Severe: list as many as possible
Signs
Mild: nausea, vomiting, lethargy
Severe: muscle cramps, weakness, confusion, ataxia, tremors
Signs: decreased level of consciousness, cognitive impairment, seizures, etc
siADH DIAGNOSIS What would serum and urine sodium be? Hence, plasma and urine osmolality? Which -volaemia? Why test with saline?
Serum sodium low
Urine sodium high
Plasma osmolality low
Urine osmolality high
Normally, euvolaemic
Test with saline - may just be sodium deficient, especially elderly
siADH management
Principle?
Diet change?
Two drugs?
Treat underlying cause
Restrict fluid intake and increase sodium intake
ORAL DEMECLOCYCLINE - induces nephrogenic DI
ORAL TOLVAPTAN - V2 blocker, very expesnive
Diabetes Insipidus can be defined as…
Number?
Large volume of dilute urine produced, due to impaired water reabsorption
>3L per day
Two categorical causes of DI with examples?
Cranial DI: decreased ADH
idiopathic, congenital, hypothalamic disease, pituitary tumour, sarcoidosis
Nephrogenic DI: can’t bind or kidney damage
CKD, metabolic disorders, gene mutations, drugs
Clinical presentation of DI?
Differential diagnosis?
Polyuria, nocturia, polydipsia, general dehydration
NO GLYCOSURIA
Rules out main ddx: diabetes mellitus
Also: hypokalaemia and hypercalcaemia
Two diagnostic tests for DI?
Fluid Deprivation Test:
Urine osmolality will stay low
IM DESMOPRESSIN (ADH analogue)
Cranial DI: will be fixed
Nephrogenic DI: won’t be fixed
How to treat cranial DI vs nephrogenic DI?
Cranial: give desmopressin, find cause, stop it
Nephrogenic: find cause and stop it, high dose desmopressin, diet control, NSAIDs & Bendroflumethiazide (both inhibit ADH)
PARATHYROID BACKGROUND
What cells produce parathyroid hormone (PTH)?
What are the 4 actions of PTH?
Chief cells
- Calcium absorption in stomach increased
- Calcium reabsorption in kidney increased (phosphate decreases)
- Calcium resorption in bone increased
- Involved in activation of vitamin D (same actions as PTH)
What are the 5 main causes of hypercalcaemia?
- Hyperparathyroidism & parathyroid disorders
- Hypercalcaemia of malignancy
- Granulomatous lung diseases (tuberculosis and sarcoidosis)
- Medications (diuretics) & dietary supplements
- Dehydration
What is hypercalcaemia of malignancy?
Why does it occur? 3 reasons
Common metabolic abnormality seen in cancer patients
Parathyroid hormone related protein is produced
Local osteolysis
Tumour production of calcitriol
Symptoms of hypercalcaemia? Name as many as possible
Polydipsia, polyuria, tiredness, headaches, nausea, muscle twitches, kidney stones,
Note: can be asymptomatic
3 types of hyperparathyroidism?
How is each treated?
How is a diagnosis made?
Primary: increase in PTH due to parathyroid tumour
(1: fluid intake, 2: parathyroidectomy)
Secondary: insufficient vitamin D or renal failure leading to hypocalcaemia and hyperplasia to produce more PTH
(treat cause)
Tertiary: fixed secondary hypocalcaemia, but continued PTH secretion due to hyperplasia
(1: fluid intake, 2: parathyroidectomy)
Dx: calcium and PTH levels, scans - Sestamibi
2 types of parathyroid tumour? Which is more common?
Parathyroid adenoma: benign tumour, often functional causing primary hyperparathyroidism
Parathyroid carcinoma: rare malignant neoplasm (>1% of parathyroid disease)
Cells in the islets of Langerhan:
Names, what they produce, percentage
Beta, insulin, 70%
Alpha, glucagon, 20%
Delta, somatostatin, 8%
F?, polypeptide secreting cells
Mechanism of insulin secretion?
Glucose binds to beta cells
Phosphorylation into glucose-6-phosphate and ATP formed from ADP
K+ channels close, causing depolarisation
Calcium channels open, and influx, causes insulin release
3 quantitative diagnostic factors for diabetes mellitus?
What is used for borderline cases?
Random plasma glucose >11 mmol/L Fasting plasma glucose >7 mmol/L HbA1c >48 mmol/mol
Impaired glucose tolerance test for borderline cases
What is the stress effect on insulin and glucagon by cortisol?
Inhibits insulin
Activates glucagon
More glucose available to the body
What is the mechanism for type 1 DM?
Associated with which HLA genes?
Inhibited insulin secretion or insulin sensitivity
Beta cells express HLA antigens, auto-immune destruction, beta cell loss, impaired insulin secretion
HLA-DR3, HLA-DR4
Impaired insulin secretion
Major symptoms of DM?
Type 1 specific?
Is type 2 normally symptomatic?
Polydipsia (thirst)
Polyuria/Nocturia (excessive urine)
Glycosuria (glucose in urine)
T1 SPECIFIC:
Weight loss despite polyphagia
Fatigue and irritability
What is metabolic syndrome?
Increased risk of…?
medical term for a combination of diabetes, high blood pressure (hypertension) and obesity
Stroke and heart disease
KETOACIDOSIS: Who does it occur in? Basic mechanism? 3 ketones? Signs? Treatment?
T1 diabetics
No insulin -> uncontrolled lipolysis -> FFA’s oxidised into ketone bodies
Acetoacetate, Acetone, Beta-hydroxybutyrate
Signs: hypotension, tachycardia, Kussmaul breathing, ketone breath, dehydration
Treatment: rehydration slowly, insulin, replacement of electrolytes
HHS: What does it stand for? Who does it occur in? Mechanism? Overlap with ketoacidosis? Treatment overlap?
Hyperosmolar hyperglycaemic state
Occurs in T2 DM
Dehydration with high glucose concentration in blood, acting as a solute
Does overlap with ketoacidosis, same treatment: rehydration, insulin and replacement of electrolytes
How is T1 DM treated?
What are the complications of the major treatment?
Education, healthy diet, regular activity, BMI control, BP and hyperlipidaemia control
INSULIN
Complications of insulin therapy:
Hypoglycaemia, lipohypertrophy of injection site, weight gain, insulin resistance, lifestyle issues
3 major risk factors for T2 DM?
Obesity, physical inactivity, family history
Complications of uncontrolled diabetes?
2 categories and examples from each
Microvascular: diabetic retinopathy, diabetic nephropathy, diabetic peripheral neuropathy
Macrovascular: CV disease and stroke
T2 diabetes control ladder?
Lifestyle change
Metformin
Metformin + Sulfonylurea
Metf + Sulf + Insulin (increase as per severity)
T2 DM Medications: class, main example, mechanism, side effect, weight gain or loss?
(4)
BIGUANIDE: metformin
increases insulin sensitivity and inhibits gluconeogenesis,
sickness and diarrhoea
Weight loss
SULPONHYLUREA: gliclazide
stimulate insulin release by closing K+ pump on beta cells,
hypoglycaemia
Weight gain
DPP4 INHIBITORS: sitagliptin stimulate incretins (hormones released after eating, which stimulate insulin release) No weight change
GLITAZONES: pioglitazone
enhance uptake of fatty acids and glucose (more fat made)
Weight gain
4 other types of diabetes?
Maturity-onset diabetes of the young (MODY)
Gestational diabetes
Drug-induced diabetes
Neonatal diabetes
Hypoglycaemia:
Measurement in blood?
Symptoms?
Whipple’s triad?
Roughly <3.9mmol/L
Trembling, palpitations, sweating, anxiety, confusion, hunger
Low blood glucose, symptomology, relief after treatment
What are carcinoid tumours?
Where are the often found?
Prognosis and signs?
Treatment?
Slow growing tumours of neuroendocrine cells (enterochromaffin cells)
Often found in GI tract, also: ovary, testes, bronchi
Bad prognosis, heart failure and bronchoconstriction
Can cause: CARLOAD CRISIS (mediators flood out)
Treatment: octreotide (somatostatin analogue)
Two major puberty disorders?
Precocious puberty - secondary sexual characteristics appear before 8 y/o in girls and 9 y/o in boys (GNRH dependant or independent)
Delayed puberty -
lack of any pubertal signs by the age of 13 y/o in girls and 14 y/o in boys
Tanner stages: boys
1 - testicular size increases
2 - sparse pubic hair, increase in testicular size (>3ml)
3 - thicker hair, spreads to mon pubis, penis growth
4 - further enlargement, dark scrotal skin colour, not spreads to medial thighs
5 - adult size and shape, spread to medial surface of thighs
Tanner stages: girls
1 - no pubic hair, elevation of papilla
2 - breast bud, enlargement of areola, pubic hair
3 - darker, coarse hair, further enlargment
4 - thick adult hair, not spread to thighs, areola and papilla secondary mound
5 - adult size and shape, just papilla projected
