Endocrine Pathology Flashcards
What is osmotic demyelination syndrome a result of?
SIADH being corrected too quickly
How is SIADH treated?
- Fluid restriction
- Salt tablets
- IV hypertonic saline
- Diuretics
- ADH antagonists (e.g. conivaptan, tolvaptan, demeclocycline)
What does the body respond to water retention with?
- Decreased aldosterone
- Increased BNP and BNP
- Increased urinary Na+ secretion
What are the different causes of SIADH?
HELD
- Head injury/CNS disorders
- Ectopic ADH (e.g. SCLC)
- Lung disease
- Drugs (SSRIs, carbamezpine, cyclophosphamide)
What is diabetes inspidus characterised by?
What is the urine osmolarity?
- Large amounts of dilute urine
- Urine osmolarity usually <300mOsm/kg
What are the 2 types of Diabetes Inspidus?
- Central DI (decreased ADH release)
- Nephrogenic DI (ADH resistance)
What are the possible causes of primary polydipsia (excessive water intake)?
- Psychiatric illness
- Hypothalamic lesions affecting thirst centre
What are causes of central DI?
- Idiopathic
- Tumours (e.g pituitary)
- Infiltrative diseases (e.g sarcoidosis)
- Trauma
- Surgery
- Hypoxic encephalopathy
Hoe is central DI treated?
Desmopressin
What are the causes of nephrogenic DI?
- Hereditary (ADh receptor mutation)
- Drugs (lithium, demeclocycline)
- Hypercalcemia
- Hypokalemia
In what type of DI is desmopressin effective?
Central (causes a significant increase in urine osmolarity ~ 50%)
How is Nephrogenic DI treated?
- Underlying cause treated
- Low solute diet
- HCTZ (diuretic)
- Amiloride (diuretic)
- Indomethacin (NSAID)
What are the different causes of hypopituitarism?
- Empty Sella syndrome (atrophy/compression, often idiopathic)
- Sheehan syndrome (Infarct, postpartum)
- Pituitary apoplexy (hemorrhage)
- Brain injury
- Radiation
What are the symptoms/signs of Sheehan syndrome?
- Ischemic infarct of pituitary following postpartum bleeding; pregnancy-induced pituitary growth increases susceptibility to infarction
- Presents w. failure to lactate, absent menstruation
- Cold intolerance
What are the causes of empty sella syndrome?
- Atrophy or compression of pituitary
- Often idiopathic, associated w. idiopathic intracranial hypertension
- Common in obese females
How can hypopituitarism be treated?
- HRT (corticosteroids, thyroxine, sex steroids, GH)
What is the most common cause of death in gigantism?
HF
What are the signs of acromegaly?
- Large tongue w. deep furrows
- Deep voice
- Large hands and feet
- Coarsening of facial features w ageing
- Frontal bossing (forehead enlarged)
- Diaphoresis (excessive sweating)
- Impaired glucose tolerance (insulin resistance)
- Hypertension
- Possible colorectal polyps and cancer
How is acromegaly diagnosed?
- Increased serum IGF-1
- Failure to suppress serum GH following oral glucose tolerance test
- Pituitary mass seen on brain MRI
How is acromegaly treated?
- Pituitary adenoma resection
- Treat with octreotide (somatostatin analog) (if not cured)
- Pegvisomant (GH receptor antagonist)
- Dopamine antagonist (cabergoline)
What are rarer causes of DM?
- Unopposed secretion of GH and epinephrine
- Patients on glucocorticoid therapy
What are small vessel diseases due to in DM?
diffuse thickening of basement membrane
What are the diagnostic cutoffs for fasting plasma glucose?
> 126 mg/dL after fasting for > 8 hours
Describe the 2 hour oral glucose tolerance test
> 200 mg/dL 2 hours after consumption of 75g of glucose in water
What is required to diagnose diabetes from a random plasma glucose?
> 200mg/dL and presence of hyperglycemic symptoms
What is found on histology in type 2 DM?
Islet amyloid polypeptide (IAPP) deposits
What is found on histology in type 1 DM?
Islet leukocyte infiltrate
What destroys Beta cells in type 1?
Autoimmune T-cell-mediated destruction of Beta cells (eg due to presence of glutamic acid decarboxylase antibodies)
What is the genetic predisposition to diabetes like in type 1 and type?
- 50% concordence in identical twins in type 1
- 90% concordance in identical twins in type 2
What is the association between type 1 and HLA system?
HLA-DR4 and DR3
What are the causes of increased cortisol ?
- Exogenous corticostroids (decreased ACTH, bilateral adrenal atrophy), most common cause
- Primary adrenal adenoma, hyperplasia, or carcinoma decreases ACTH and atrophy of uninvolved adrenal gland
- ACTH screting pituitary
What are the findings in Cushing syndrome?
- Incr Cholsterol
- Incr Urinary free cortisol
- Skin changes (thinning striae)
- Hypertension
- Immunosuppression
- Neoplasm
- Growth restriction (in children)
- Increased Sugar (hyperglycemia, insulin resistance)
- Moon facies, amenorrhea, buffalo hump, osteoperosis, incr weight (truncal obesity), hirsuitism
How is cushing’s diagnosed?
- Increased free cortisol on 24-hr urinalysis
- Increased late night salivary cortisol, and no suppression with overnight low-dose dexamethasone test
What is Nelson syndrome?
Enlargement of pre-existing ACTH-secreting pituitary adenoma after bilateral adrenalectomy for refractroy Cushing disease
- Presents with increased ACTH (hyperpigmentation), mass effect (headaches, bitemporal hemianopia)
How is Nelson syndrome treated?
- Transsphenoidal resection
- Postoperative pituitary irradation for residual tumour
What are the symptoms of adrenal insufficiency?
- Weakness
- Fatigue
- Orthostatic hypotension
- Muscle aches
- Weight loss
- GI disturbances
- Sugar/salt cravings
How is adrenal insuffficiency treated?
Glucocorticoid/ mineralcorticoid treatment
What types of hypercortisolemia has decreased ACTH levels?
- Exogenous steroids
- Adrenal tumour
What types of hypercortisolemia have increased ACTH levels?
- Pituitary adenoma (Cushing’s)
- Ectopic ACTH secretion
How can ectopic and Cushings hypercortisolemias be differentiated?
- Ectopic cause will not have suppressed ACTH after dexamethasone adminstration - Cushings will
- CRH stimulation test will cause increased ACTH in Cushing’s and no effect in Ectopic
- MRI can show pituitary tumour
- CT of chest/abdo pelvis can show ectopic ACTH secreting gland
What is MSH a biproduct of?
POMC cleavage
What are the causes of Addisons disease? (primary adrenal insifficiency)
- Autoimmune adrenalitis (developed world)
- TB (developing world)
What is the eitiology behind acute adrenal insufficiency? (adisonian crisis)
- Acute stressors that increase steroid requirements (e.g. infection)
- In patients with preexisting adrenal insufficiency or on steroid therapy
What may acute adrenal insuffciency (addisonian crisis) present with?
- Acute abdomen
- N/V
- Altered mental status
- Shock
What is Waterhous-Friderichsen syndrome?
Bilateral adrenal hemorrhage often due to meningococcemia
- May present with w acute adrenal insufficicnecy, fever, petechiae, sepsis
Why does hyperpigmentation not occur in secondary and tertiary adrenal insufficiency?
Decreased ACTH is the cause of secondary adrenal insufficiency
- Decreased CRH and then ACTH in the case of tertiary
ACTH is thr hormone responsible for the hyperpigmentation
Why is there no hyperkalemia in secondary and tertiary adrenal insufficiency?
Adrenal gland is functioning and intact so aldosterone sysnthesis is and therefore intact RAAS and no hyperkalemia
What is tertiary adrenal insufficiency most commonly due to?
Abrupt cessation of chronic steroid therapy
Tertiary from Treatment
What are the levels of aldosterone and renin in primary hyperaldosteronism?
- Aldosterone increased
- Renin decreased (treatment resistant)
What can secondary hyperaldosteronism be due to?
- Renovascular hypertension
- Juxtaglomerular cell tumours (renin-producing)
- Edema (cirrhosis, HF, Nephrotic syndrome)
What are examples of neuroendocrine tumours?
- GI system - Carcinoid, gastrinoma
- Pancreas - Insulinoma, glucagonoma
- Lungs - SCLC
- Thyroid - Medullary carcinoma
- Adrenals - Pheochromocytoma
What do neuroendocrine tumours share a common biologic function through?
Amine precursor uptake decarboxylase (APUD)
How may neuroendocrine tumours be treated?
- Surgery
- Somatostatin analogs (octreotide)
What is the most common tumour of the adrenal medulla in children < 4 yrs old?
Neuroblastoma
What cells does neuroblastoma originate from?
Neural crest cells
What is the most common presentation of neuroblastoma?
- Abdominal distension
- Firm, irregular mass
- Mass can cross midline
- opsoclonus-myoclonus syndrome (dancing eyes-dancing feet)
What can differentiate between neuroblastoma and Wilms tumour?
- Wilms tumour is unilateral cannot cross midline and is smooth
- Neuroblastoma is irregular mass that can cross midline
What is more likely to develop hypertension neuroblastoma or pheochromocytoma?
Pheochromocytoma
What can be found in urine in neuroblastoma?
HVA and VMA (catecholamine metabolites)
What can be seen on histology in neuroblastoma?
Homer-Wright rosettes (neuroblasts surrounding a central lumen)
- Bombesin and NSE +ve
What oncogene is amplified in neuroblastoma?
N-myc oncogene
What are the symptoms/signs of pheochromocytoma?
EPISODIC hyderadrenergic symptoms (5 Ps)
- Pressure (hypertension)
- Pain (headache)
- Perspiration
- Palpitations (tachycardia)
- Pallor
May secrete EPO -> polycythemia
What is the rule of 10s in relation to pheochromocytoma?
10%:
- Malignant
- Calcify
- Bilateral
- Kids
- Extra-adrenal (bladder wall, organ of Zuckerkandl)
What substances can be found in urine and plasma of pheochromocytoma patients?
- HVA (Homovanillic acid)
- VMA (vanillylmandelic acid)
What is pheochromocytoma positive for?
- Chromogranin
- Synaptophysin
- NSE
How is pheochromocytoma treated?
- Alpha1 blockers (phenoxybenzamine)
- Beta blockers
- Tumour resection
What does somatostatin in somatostatinoma cause a decrease of (in relation to hormones)?
- Decreased secretin ]
- CCK
- Glucagon
- Insulin
- Gastrin
- Gastric inhibitory peptide
What will stomatostatinoma present with?
- Diabetes/glucose intolerance
- Steatorrhea
- Gallstones
- Achlorydia (lack of HCl)
What are the 6 Ds associated with glucagonoma?
- Dermatitis (necrolytic migratory erythema)
- Diabetes (hyperglycemia)
- DVT
- Declining weight
- Depression
- Diarrhoea
What is the treatment of glucagonoma?
Octreotide/soamtostatin analog and surgical resection
What are the symptoms associated with carcinoid syndrome?
5-HT in systemic circulation
- Episodic flushing
- Diarrhoea
- Wheezing
- R sided valvular heart disease (e.g tri regurg, pulmonic stenosis)
- Niacin deficiency (pellegra)
What can be seen on histology in carcinoid tumour?
- Prominent rosettes
- Chromogranin A positive
- Synaptophysin positive
How is a carcinoid tumour treated?
- Surgical resection
- Somatostatin analog
- Tryptophanhydroxylase inhibitor (e.g. telotristat) for symptom control
What do neuroendocrine cells secrete in carcinoid tumours and how can this enter systemic circulation to cause carcinoid syndrome?
5-HT - can bypass hepatic first pass metabolism and enzymatic breakdown from MAO in lung by metastasising to the liver
What is the rule of 1/3 in relation to carcinoid tumours?
- 1/3 metastasise
- 1/3 present with 2nd malignancy
- 1/3 are multiple
What is Zollinger-Ellison syndrome due to?
Gastrin-secreting tumour (gastrinoma) of duodenum or pancreas
- Causes acid hypersecretion -> recurrent duodenal and jejunal ulcers
What can ZE syndrome present with?
- Abdo pain (peptic ulcer disease, distal ulcers)
- Diarrhoea (malabsorption)
How can Zollinger Ellison syndrome be diagnosed?
Positive secretin stimulation test:
- Increased gastrin levels after administration of secretin, which normally inhibits gastrin release
