Week 9 Endoncrinology Flashcards
Pituitary tumours
Non-functional (most common) - don’t secrete hormones
Cause: Bitemporal hemianopia
Headaches
Functional - secrete hormones
Prolactinoma (most common)
GH adenoma - acromegaly
TSHoma
ACTH - Cushing’s
Prolactinoma
Pituitary tumour that secretes prolactin
Symptoms: - Golactorrhoae and ammenorrhoea (as prolactin causes decreased GnRH hence decreased LH, FSH)
- Decreased libido in males
- Headaches
Investigations:
Serum prolactin
MRI pituitary
Treatment:
Dopamine agonists e.g. bromocriptine, carbergoline
Surgery
Acromegaly
Pituitary tumour secreting GH
Other causes: GH cell adenoma, MEN 1, Increased GHRH (ganglioneuroma)
Gigantism in children
Acromegaly in adults
Symptoms:
Increased size in hands/feet, cardiomyopathy (LV dysfunction decreased), peripheral neuropathy, HTN
Increased inter-dental spaces Investigations:
Glucose tolerance test (as glucose normally suppresses GH)
IGF-1 levels (increased in acromegaly)
MRI Treatment:
1st line: surgery
Somatostatin analogues
- Ocreotide
GH receptor antagonists - Pegvisomant
Cushing’s disease
Pituitary tumour secreting ACTH
Main cause of Cushing’s syndrome
Symptoms: moon face, weight gain, thin skin, increased BP
Diagnosis:
Dexamethasone suppression test
Treatment:
1st line: surgery
Bilateral adrenalectomy
Ketoconazole Radiotherapy
TSHoma
Pituitary tumour releasing TSH
Causes increased T4
Hypopituitarism
Tumour - Pituitary adenoma
Radiotherapy
Infarction/haemorrhage (apoplexy)
- post partum: Sheehan’s syndrome
ADH
Post. pituitary
Diabetes insipidus
ADH deficiency (cranial or nephrogenic - due to impaired renal response to ADH))
Cranial
Causes:
Idiopathic
Pituitary tumour
Trauma
Sarcoidosis
Investigations
Water deprivation test (unable to concentrate urine)
Treatment: Desmopressin (analogue ADH)
Anterior Pituitary
GHRH - GH - Somatotrophs (50%) - multiple organs
GnRH - LH/FSH - Gonadotrophs (10-%) - ovaries/testes
CRH - ACTH - Corticotrophs (10%) - adrenal gland
TRH - TSH - Thyrotrophs (5%) - thyroid gland
Prolactin - dopamine (-ve) - Lactotrophs (20%) - breast/uterus
Follicular cells (produce T3 and T3)
Parafolliclar cells secrete calcitonin
Colloid (thyroglobulin) in middle
Actions of thyroid hormones
Increaeses metabolic rate
Increases glucose, protein synthesis
Grwoth and development
Increases catecholamine effect
Hypothyroidism
Causes: Iodine deficiency (common cause worldwide)
Iatrogenic - radiotherapy, drugs e.g. litium, amiodarone
Congenital hypothyroidism/cretinism
Pituitary macroadenoma
Clinical features: developmental delay, large fontenelle, dry skin
Autoimmune - Hashimoto’s thyroiditis (autoimmune disease leading to destruction of thyroid gland)
Symptoms:
Cold interolance, Weight gain, Constipation, Goitre (swelling in neck due to enlarged thyroid) , Heavy menstrual periods
Signs:
brittle hair with loss of outer eyebrows, dry skin, bradycardia, cold peripheries
Investigations
TSH, T4, (T3 unhelpful as there is increased conversion of T4 to T3)
Primary hypo: High TSH, Low T3/T4
Secondary hypo: Low/normal TSH, Low T3/T4
Subclinical hypo: High TSH, Normal T3/T4
Antibodies (Hashimoto’s)
Anti-thyroglobulin antibody
Anti-tyrosine perxodiase antibidy
US goitre
Treatment: Levothyroxine (acts like T4, gets converted into T3. Increases metabolic rate of all tissues)
Side effects: Tacycardia, chest pain, diarrhoea
Hyperthyroidism
Primary causes (due to thyroid):
Grave’s disease
Toxic multinodular gotire
Toxic adenoma
Secondary:
Pituitary adenoma - TSHoma
Gestational thyroxcisos - high hCG
Drugs - amiodarone:
- inhibits conversion T4 to T3 (leads to increased TSH)
- causes hypothyroidism
- causes hyperthyroidism by Jod Basedow (due to increaesed iodine) or destructive thyroiditis
Grave’s:
Autoimmune disease where IgG stimulates TSH receptor of the thyroid gland, causing T4 release
- Triad of thyroid eye disease (peri-orbital oedema, proptosis, lid retraction), gotire, thyrotoxicosis
- Pretibial myoxedema (thyroid dermopathy)
- Clubbing (thyroid acropachy)
- Smooth, diffuse gotire
Symptoms: Weight loss, heat intolerance, diarrohea, ammenorhoea, anxiety
Signs: Tremor, Tachycardia, sweaty skin
Investigations:
Primary: low TSH, T3/T3 high
Secondary: high TSH: T3/T4 high
Subclinical hyperthyroidism: low TSH, Normal T3/T4
TSH receptor antibodies
TPO antibody
Iodine (I23) uptake scan
Diffuse with reduced backgroud: Grave’s
Irregular - toxic multinodular goitre
Hot nodule - toxic adenoma
Reduced uptake - Thyroiditis
Treatment:
Carbimazole/Propylthiouracil:
- Inhibits production of tyrosine peroxidase, required for production of thryoid hormones and inhbits conversion of T4 to T3
PTU used if pregnancy planned/pregnant
Side effects: agranulocytosis, rash
Beta-blocker e.g. propanolol
Radioactive iodine - contraindicated in pregnancy, lactation, tyroid eye disease
Indicated for toxic multinodular goitre
Surgical - failed medical treatment
Complications: hypothyroidism, recurrent laryngeal damage (hoarse voice), damage parathyroid glands (hypocalcaemia)
Iodine induced hypo and hyperthyroidism
Jod Basedow - iodine induced hyperthyroidism
Wolff Chaikoff - iodine induced hypothyroidsm
Amiodarone
Type I - Autoimmune thyrotoxicosis (increase thyroid hormone synthesis due to increaesd iodine)
Treatment: High dose carbimazole
Type II - destructive thyroiditis (desrtruction thyroid gland leading to T3/T4 release)
Treatment: Glucocorticoids
Thyroid cancer
Follicular cell - benign adenoma, follicular cancer
Cancer of parathyroid cells - medullary cancer
familail medullary thyroid ca. - assoc with RET (proto-oncogene)
PTH
Stored in chief cells of parathyroid gland
Controlled by calcium sensing receptor (CaSR)
When there is increased Ca:
- inhibits secretion of PTH
- increases breakdown of PTH
Loss of function assoc. with familaim hypocalciuric hypercalcaemia
- increases Ca2+ and Mg2+ excretion in kidneys
- stimulates calcitonin release in thyroid gland
Hyerpcalcaemia
PTH mediated (high Ca2+, high PTH)
Primary hyperparathyroidism
Familial hypocalciuric hypercalcaemia
PTH independent (high Ca2+, low PTH)
Malignancy
- osteolytic metastases
- tumour secreting PTHrP e.g. squmous cell lung carcinoma
- tumour secreting Vit D e.g. lymphoma
Vit D toxicity (increases bone resorption, gut absorption)
Drugs e.g. thiazide
Milk-alkali syndrome (taking too much Ca2+. Hypercalcaemia, renal insuffiency, metabolic alkalosis)
Symptoms:
Moans - confusion
Groans - abdo pain, short QT
Stones - nephrolithiasis
Bones - bone pain
Treatment:
Rehydration (dilute Ca2+ level)
Loop diuretics (with saline to increase excretion of Ca2+)
Bisphosphonates (inhbits bone resorption)
Calcitonin (increases urinary Ca2+ excretion)
Steroids (Vit D toxicity)
Primary hyperparathyroidism
Causes: Parathyroid adenoma
Parathyroid hyperplasia - assoc. with MEN
Common in post menopausal women
End-organ damage:
Bone - OP
Kidneys - nephrocalcinosis
Can cause brown tumours - collection of osteoclasts leading to poorly mineralised bone, brown due to haemosiderin deposition
Investigations
U and Es, PTH, urine calcium:creatnine ratio, Vit D
Treatment
1st line: Parathyroidectomy
Complications: vocal cord paresis, haematoma compressing trachea
Bisphosphonates
Cinalcalet (calcium sensing receptor agonist. Decreases PTH, decreases serum calcium)
Vit D deficiency
Causes:
Decreased sunlight exposure
Malabsorption
Renal disease - (as can’t hydroxlyate 25-OH)
Osteomalacia
Assoc with decreased vit D
Can’t ossify adult bones
Symptoms: bone pain, proximal myopathy, hypocalcaemia
Low Ca, ALK phos, Vit D
High PTH
Treatments:
Cholecalciferol
Alfacalcidol (active D3) - for renal impairment, hypoparathyroidism
Cushings syndrome
Excess cortisol secretion
Symptoms:
Moon face, buffalo hump, abdo striae, weight gain, hyperglycaemia
Causes:
Iatrogenic: excess steroids (leads to atrophy of adrenal glands due to decreased ACTH)
ACTH dependent:
Pituitary adenoma
Paraneoplastic ACTH secretion e.g. small cell carcinoma of lung
ACTH independent:
Adrenal adenoma
Adrenal carcinoma
Adrenal hyperplasia
Investigations
24 hour urinary free cortisol
Late night salivary cortisol (should be undetectable)
Dexemethasone test (supresses ACTH from pituitary tumour, but not ectopic ACTH (due to carcinoma)
Management:
Adrenalectomy
Ketoconazole
Congenital adrenal hyperplasia
Autosomal recessive due to defect in steroidgenic genes
Lack of CYP21 (21 alpha hydroxylase)
Deficiency in cortisol, aldosterone
Increase in androgens
Females: ambigous genatalia
Males: Adrenal crisis
Treatment
Mineralcorticoid, glucocorticoid
Adrenal cortex
Glomerulosa - Aldosterone
Fascularis - Cortisol
Reticularis - Androgens
Medulla: Chromaffin cells - Catecholamines
Aldosterone:
Mineralcorticoid
Stimulates Na2+ absorption (hence H2O)
Excretion K+, H+
Cortisol:
Stress leads to activation of hypothalamus secreting CRH - ACTH - cortisol
Stimulates gluconeogenesis, lipolysis, supresses insulin release, immune suppression
Primary and seondary aldosteronism
Commonest secondary cause of HTN
Primary (suppressed renin):
Adrenal adenoma (Conn’s syndrome) or bilateral adrenal hyperplasia, adrenal carcinoma
Biochem:
Raised Na, decreased K+
ARR (aldosterone-renin ratio) increased
Increased aldosterone, decreased renin
Clinical features:
HTN, hypokalaemia, alkalosis
Treatment:
Stop B-blockers (causes increased ARR)
Saline suppression test: Give saline, aldosterone should not be high
MR antagonists: Spironolactone
Surgical - only if adrenal adenoma
Secondary aldosteronism (increaed renin)
HF, cirrhosis of liver, nephrotic syndrome, liqorice ingestion
High renin and aldosterone
Adrenal insufficiency
Decreased aldosterone and cortisol
Primary:
Addison’s disease - primary adrenal insuffieciency, affects adrenal glands, leading to decreased aldosterone and cortisol
Causes: TB (most common cause worldwide), autoimmune, metastatic cancer (e.g. colonic carcinoma), adrenal haemorrhage, drugs (ketoconazole)
Symptoms:
Fatigue, anorexia, GI symptoms e.g nausea and vomiting, salt craving
Signs: Weight loss, hyperpigmentation (sun-exposed areas and mucosa), postural hypotension,
Biochemistry:
Anaemia, eosinophilia
Decreased Na, Increased K+
Hypoglycaemia
Decreased aldosterone, increased renin
Increased ACTH
Investigations
Short synacthen test: give ACTH, and see if levels increase
Adrenal autoantibodies
Treatment:
Hydrocortisone (good glucocorticoid activity and mineralcorticoid activity)
Fludrocortisone potent mineralcorticoid activity. Mild glucocorticoid activity)
SE: hyperglycaemia, immunodeficiency, Cushing’s, gastric irritation (need to take with food)
Other points: don’t stop abuptly, take high dose when ill, carry steroid card)
Secondary (Due to pituitary)
Panhypopituitarism - pituitary tumours, TB, sarcoidosis
Tertiary (hypothalamus)
- Chronic high dose glucocorticoids
Localisation of cortisol source (if high)
plasma ACTH (if low, then adrenal)
Dexamethasone suppression test
- Pituitary tumours respond (cortisol will decrease), ectopic tumours don’t
CRH test
Pituitary tumours respond, ectopic tumours don’t
CT or MRI adrenal
Ammenorrhoea
Primary
Rokitansky syndrome (no uterus)
Turners syndrome
Secondary (due to piuitary)
Kallmans
Ashermans syndrome
PCOS
Pregnancy, iatrogenic - OCP
Hirsutism
Excess hair growth in male pattern due to increased androgens
Causes:
PCOS, congenital adrenal hypertrophy, androgen secreting tumour
PCOS
Annovulation (ammenorrhoea) , and hyperandrogenism (hirsutism, ance)
Usually presents inn adolescence
Assoc. with metabolic syndromes e.g. TMD2
Pathophysiology
Gonadotropins
Increaesd LH, decresaed FSH
Androgens
Increased androgen production from theca cells under LH
Decreased SHBG (sex hormone binding globulin) which binds testosterone (only free testosterone is active)
Insulin resistance
Increased insulin secretion, which stimulates theca cells
Reduces SHBG production
Increases circulating androgens
Investigations
Testosterone
DHEAS
SHBG
LH/FSH
Treatment:
Metformin (only for those at high risk of developing diabetes)
COCP (suppresses ovarian production of androgens)
Corticosteroids (suppresses adrenal production of adrogens)
Spironolactone (MR anatagonist)
Hypogonadism
Clinical syndrome of symptoms/signs and biochemistry of testosterone deficiency
Symptoms:
No pubertal growth spurt
Delayed growth
Decreased libido
Erectile problems
Investigations
Testosterone (early morning)
SHBG
LH/FSH - determine if primary or secondary
Primary hypogonadal hypogonadism
- Decreased testosterone, N/increased LH/FSH
Normal prolactin
Increased oestrogen
Causes: Klinefelter’s, Leydig cell failure (due to chemo)
Klinefelter’s syndrome
XXY (karyotype 47)
Decreased testosterone, increased LH/FSH (but leydig cells dont work properly)
Clinical features:
Gynaecomastia
Delayed puberty
Azospermia
Treatment:
Androgen replacement therapy
Side effects: libido issues, mood issues
hcG, recombiant LH/FSH
Secondary hypogonadal hypogonadism
Low testosterone, low LH/FSH
Decreaed cortisol, IGF, TSH, increased Na+
Causes: Kallman’s syndrome, Pituitary tumour, Cerebellar ataxia
Kallman’s syndrome
Failure of migration of GnRH cells to hypothalamus from olfactory placode
Aplasia of olfactory lobes - anosmia
Symptoms:
Slow growth, micro penis, cryptorchidism, assoc. with deafness
Famlial:
KAL 1 - X linked rec
KAL 2 - AD
KAL 3 - AR
Thyrotoxicosis vs. hyperthyroidism
Thyrotoxicosis: Excess T4 and/or T3 thyroid hormones in body
Hyperpthyroidism: overactive thyroid gland due to thyrotoxicosis
Eye signs specific to Grave’s opthalmopathy
Redness, grittiness
Periorbital oedema
Opthalmoplegia (weakness of eye muscles)
Proptosis /exopthalmos (bulging of eye anteirorly)
Lid retraction
Treatment Grave’s eye disease
Artificial tears
Eyelid tape
Steroids
Myxodema
Severe hypothyroidism where there is an accumulation of mucopolysaccharides of dermis leading to thickened skin
Signs:
Expressionless face
Pale skin
Cerebellar ataxia
Pericardial effusion
Myxoedema coma - reduced conciousness and hypothermia. Reduced BP, hyponatraemia
Treated with IV fluid, slow rewarming, IV T3
Non diabetes related hypoglycaemia
Hypoglycaemia: <4 in diabetics, non diabetics: <3
Whipple’s trad:
Low blood glucose
Symptoms of low blood glucose (sweating, palpitations, headache, confusion)
Relief of symptoms after glucose
<4.6 - inhibtion of insulin
<3.8 - release counter-regulatory hormones e.g. glucagon - leads to symptoms e.g. sweating, palpitations
<2.5 - impaired congitive function - confusion
< 2 - EEG changes
<1.5: coma
Investigations of hypoglycaemia
Glucose
Insulin
C peptide
B-hydroxybutyrate (low in insulinoma)
72 hours fast
Imaging - CT
Arterial Ca2+ stimulation: Differentiated between insulinoma and diffuse disease (Ca2+ causes insulin release from insulinoma)
Causes of spontaenous hypoglycaemia
Insulinoma
Islet cell disorder, not insulinoma- nesidioblastoma
Non islet cell tumour
Drugs - lithium, trimethoprim
Endocrine - hypopituitarism
Sepsis
Anorexia
In ill people:
Drugs
Critical illness
Hormone deficiency
Healthy people:
Increased endogenous insulin e.g. insulioma
Accidental
DKA
Characterised by hyperglycaemia, metabolic acidosis, ketonaemia/ketonuria
Symptoms: polyuria, polydipsia, Kassmaul’s breathing, weight loss, abdo pain
Pathophys:
- Insulin deficiency
- increase in couter-regulatory hormones e.g. glucagon
- increase lipolysos, free fatty acid release
- FFAs are substrates for ketone production in liver
- Ketones (B-hyroxybutyrate) excreted by kidneys but eventually cant compensate - acidosis
- Gluconeogenesis occurs - hypergylcaemia - osmotic diuresis - dehydration - acidosis
Causes
New onset diabetes
Stopping insulin
Infection
MI
Pregnancy
Steroids
Substance abuse
Treatment:
IV fluids (NaCl)
IV insulin
Pottasium
Hyperglycaemic hyperosmolar state
Severe hyperglycaemia (>30 glucose), hyperosmolality and hypovolaemic without ketoacidosis
May lead to coma
Causes:
Infection, poor compliance, drugs
Treatment:
IV fluids (NaCl), insulin, LMWH ( as pt increased risk of co-agulation), foot protection
Autoimmune polyendocrine sydnrome type 2
Triad of Addison’s, TMD1, autoimmune thyroiditis
HLA DR3/4
Assoc. with coeliac, alopecia, pernicious anaemia, myasthenia gravis
(HLA DR4 assoc. with RA)
