Endocrine disorders Flashcards
What is hypopituitarism? What can cause it?
Combined def of any anterior pit hormone
- e.g. glucocorticoid def (lack of ACTH), lack of thyroid hormone (due to lack of TSH), antidiuretic hormone (cause diabetes)
Causes:
- head trauma - pituitary tumour/lesion - drug-damage - infections - post-partum necrosis - acute haemorrhage
What is secondary adrenal insufficiency and what can cause it?
Most common cause of ACTH def –> could be due to pituitary tumour
Often due to abrupt w/drawal of long-term corticosteroid therapy
What is primary adrenal insufficiency?
AKA = Addison’s disease
Rare chronic metabolic disorder –> adrenal cortical hormones are deficient –> ACTH lvls are elevated due to feedback mechanism
What hormones are produce by the adrenal cortex?
glucocorticoids
Mineralocorticoids
adrenal sex hormones
What hormones are produce by the medulla of the adrenal glans?
adrenaline
noreadrenaline
What are the sx and signs of Addison’s Disease?
Mineralocorticoid def = impaired salt/water reg
glucocorticoid def = impaired ability to ref BG, control immune and inflam response
Dehydration, abnormal appetite for salt, weakness, fatigue, depression, lethargy, fever, myalgia, arthralgia
GI sx (anorexia, N/V), hyperpigmentation/vitiligo
Cardiovascular collapse, shock
What is the aetiology of Addison’s disease?
Autoimmune
Breast cancer, metastatic carcinoma
histoplasmosis, CMV, TB
Bilateral adrenalectomy
Bilateral adrenal haemorrhage w/ anticoagulant
How are glucocorticoids used to treat Addison’s disease?
Cortisone –> converted to hydrocortisone in live = improve glucocorticoid sx
Drugs = Hydrocortisone –> maintenance therapy entails two doses to mimic natural pattern
- no concern about long-term glucocorticoid use
*inc tx 2-3 fold during any systemic illness or surgery to simulate normal inc in glucocorticoids during stress
What mineralocorticoids used to treat Addison’s disease?
Use fludrocortisone
ADRs = oedema, hypokalaemia,
DO NOT stop taking suddenly
What is an acute adrenal crisis and how is it treated?
Life-threatening = sudden or progressive due to underlying Addison’s disease problem
5’s = combination of glucocorticoids and mineralocorticoids
- Salt replacement
- Sugar (dextrose) replacement
- Steroid replacement
- Support acute physiological trigger (e.g. infection)
- Search for cause
What are some signs/sx of adrenal excess?
Euphoria, buffalo hump, HTN
Thinning skin, inc abdominal fat
Thing arms and legs, muscle wasting, mood face w/ red cheeks
Benign intracranial HTN, easy bruising, poor wound healing
What is Cushing’s syndrome and what causes it?
Glucocorticoid hormone excess = early sign is loss of diurnal variation in CRH and ACTH secretion
Causes:
- adrenal hypersecretion
- Ectopic cushing’s: non-pituitary ACTH secreting tumour
- prolonged administration of potent pharm glucocorticoids
What is a dexamethasone suppression test and when is it used?
Used to diagnose adrenal dysfunction = differentiates between types of cushing’s syndrome and hyper cortisol states
Dexamethasone provides -ve feedback to pituitary —> supress ACTH secretion
Normal result = dec in cortisol concentration
Cushing’s = no change w/ low-dose dexamethasone suppression
High dose dexa = differential diagnosis
What is the short synacthen test?
Uses Tetracosactrin – ACTH = assess adrenal gland responsiveness to exogenous ACTH
Used to diagnose adrenocortical insufficiency
Normal = generate adequate cortisol response –> >500nmol/L
Adrenal insufficiency = <495 nmol/L
How is Cushing’s syndrome treated?
Surgery for tumour plus replacement corticosteroids after
Pharm agents that block glucocorticoid synth = etomidate, mitotane, ketoconazole
May req prophylaxis therapy for prevention of possible secondary/opportunistic infections
What conditions are caused by GH deficiency and excess?
Deficiency = hypopituitary dwarfism
Excess = acromegaly/ gigantism
How is somatropin (recombinant hGh used?
Used in short stature children due to
- GH def
- Chronic renal insuff
- Turner’s syndrome
- Prader-Willi syndrome
How does somatropin/somatotropin work?
Promotes skeletal, visceral and general growth = stimulates cells to grow in size and divide more rapidly
GH metabolic effects:
- Inc lipolysis
- Promotes cellular growth through retention of phosphorus, sodium, K+
- Enhance AA transport across cell membrane and protein synthesis
- Dec cellular carb usage
- dec insulin
What is the drug therapy for growth hormone excess?
Dopamine agonists –> inhibit release of prolactin and GH
Somatostatin –> natural GHRIF - inhibits release of TSH, insulin, glucagon, GI hormones
Somatostatin analogues - octreotide, lanreotide
How is octreotide used in growth hormone inhibition of GH excess?
MOA = Inhibits release of GH and gut hormones, longer duration than somatostatin
Used in acromegaly and sx associated w/ GI pancreatic tumours
What is hyperprolactinaemia and what causes it?
Inc thyrotropin-releasing hormone as well as oestrogen = inc prolactin excretion (prolactin usually inhibited by dopamine) —-> supressed released of GnRH –> inc milk production
Potential causes:
- hypothalamic or pituitary damage –> tumours/trauma
- pregnancy, hypothyroidism, renal failure, PCOS
- Drugs: 1st gen anti-psychotics, atypical antipsychotics, methyldopa, verapamil, metoclopramide, SSRIs, TCA, oestrogens, opioids, cannabis
- Idiopathic
What are the sx of hyperprolactinaemia in men and women?
May be asymptomatic
Related to mass = headache, visual disturbances, rhinorrhoea
Female = menstrual disturbances, infertility, galactorrhoea
Male = erectile dysfunction, diminished libido, galactorrhoea, gynaecomastia
What are the goals and tx of hyperprolactinaemia?
Goals:
- restoration of fertility and eugonadism
- normalise serum prolactin levels
- Relief of other sx
Tx: Dopamine antagonist
- bromocriptine
- Cabergoline
- quinagolide
What conditions can antidiuretic hormone dysfunction cause?
Deficiency = diabetes insipidus
Excess = SIADH
