Endocrinology Flashcards
What is adrenal insufficiency?
Adrenal glands don’t produce enough hormones (cortisol +/- aldosterone)
What hormones control the release of cortisol and aldosterone from the adrenal glands?
Hypothalamus secretes CRH -> pituitary gland secretes ACTH -> release of cortisol from adrenal glands
Renin produced by kidneys -> RAAS system -> end product is aldosterone production from adrenal gland
Primary adrenal insufficiency
Labs (cortisol, aldosterone, renin, ACTH, CRH, Na, K)
Causes
Presentation
Tx
Problem with ADRENAL GLAND itself
- > low in cortisol and aldosterone
- high plasma renin activity
- > high ACTH and CRH
- > hyponatraeamia, hyperkalaemia
Causes
- Most common cause in developed world is autoimmune destruction (incr levels of serum anti-adrenal Ab (anti 21 hydroxylase) = Addisons disease
- Infection [Tb (most common cause worldwide), HIV, fungal]
- Bilateral adrenal metastases
- Bilateral adrenal infarction, haemmhorage (caused by meningococcaemia = waterhouse-friedrichson syndrome)
- Congenital adrenal hyperplasia (most common cause in infancy)
- Drugs
- Adrenoleukodystrophy - peroxisomal disorder; incr serum VLCFA
Presentation
- Hyperpigmentation of skin creases, oral mucosa due to excess ACTH
- Salt craving due to low aldosterone
- Signs of hypopituitarism
Tx - long term replacement of cortisol (hydrocort) and aldosterone (fludrocort)
Secondary adrenal insufficiency
Labs (cortisol, aldosterone, renin, ACTH, CRH)
Causes
Presentation
Results from insufficient production of ACTH from pituitary
- Low ACTH and cortisol
- Normal aldosterone (no problem w adrenals)
- High CRH (positive feedback)
Causes
- Panhypopituitarism (trauma or tumour within pituitary or compression by another tumour in vicinity)
- OR isolated ACTH deficiency (autoimmune, genetic disorders, medications)
Presentation
- headaches
- visual abnormalities
- signs of hypopituitarism
Tertiary adrenal insufficiency
What is it
Causes
Presentation
Insufficiency of CRH secretion from hypothalamus
- Low CRH, ACTH
- Low cortisol
- Normal aldosterone
Causes
- Sudden withdrawal of chronic GC therapy
- Removal of ACTH secreting tumour
- -> 1 and 2 are caused by sudden removal of high levels of EXOGENOUS circulating GC where neg feedback loop was suppressing CRH release from hypothalamus - takes a while for this neg feedback to resolve and for the hypothalamus to begin eleasing CRH again.
Other causes directly impacting hypothalamus:
- Head trauma
- Intracranial tumours
Presentation
- headaches
- visual abnormalities
- hypoglycaemia
+/- signs of panhypopituitarism
Adrenal crisis presentation
Triggered by some sort of stressor (infx/illness, surgery, trauma) in setting of adrenal insufficiency
Acute:
Hypotension, shock
Vomiting
Abdo pain
Fever
Drowsiness, Coma
Chronic:
- fatigue
- anorexia
- nausea and vomiting
- LOW/FTT
- postural hypotension and salt craving
- abdo, muscle, joint pain
IX
- metabolic acidosis
- hyperkalaemia and hyponatraemia
- hypoglycaemia
Tx
- Immediately give IV fluids (20ml/kg) and stat dose IV hydrocort followed by q6-8hrly dosing hydrocort until no longer acutely unwell
+/- IV dextrose if hypoglycaemic
Note- hyperkalaemia normally resolves with fluid and steroid tx
Investigation/diagnosis of adrenal insufficiency - what investigations would you order?
- Morning serum cortisol level to confirm diagnosis of adrenal insufficiency
a) LOW: confirms diagnosis -> proceed to measure serum ACTH levels (high: primary AI vs low: secondary/tertiary AI)
b) HIGH: excludes
c) Intermediate: proceed to ACTH stimulation test - ACTH stimulation test (involves administering synthetic ACTH ‘cosyntropin’ and measuring serum cortisol levels before and after)
- > if cortisol levels are normal before and after = AI excluded
- > If levels are low before and low after = primary AI
- > if levels are low before but increase after = secondary/tertiary - To distinguish between sec and tertiary
- CRH stimulation test (inject CRH then measure ACTH)
- > no rise in ACTH: secondary
- > Rise in ACTH: tertiary
Signs of panhypopituitarism
Presentation:
TSH: fatigue, lassitude, cold intolerance, constipation
GH: short stature, hypoglycaemia
ACTH : hypoglycaemia, vomiting, malaise
Aldosterone: Diabetes insipidus (polyuria, polydipsia, dehydration)
GH: Growth failure/short stature/FTT
LH, FSH: delayed puberty, Decr libido, Amenorrhoea
Adrenoleukodystrophy
Neurometabolic condition
Predominantly affects males age 4-8yo
VLCFA accumulate in CNS -> neurodev regression and adrenal cortex -> adrenal insufficiency
Presentation:
- Initially resembles ADHD
- Progressive impairment of cognition, behavior, vision, hearing, and motor function follow the initial symptoms
- often have impaired adrenal function at the time of neurological sx onset
- Lead to total disability within six months to two years
Female carriers
- 20% develop mild-to-moderate spastic paraparesis in middle age or later usually w normal adrenal function
Ix
- incr serum levels VLCFA
- MRI: T2 enhancement in Pareto-occipital regions
- adrenal tests
- genetic testing (mutation in ABCD1 gene)
Mx
- Life long hydrocort tx
- HSCT is an option for boys and adolescents in early stages of sx who have evidence of brain involvement on MRI
Congenital adrenal hyperplasia
What is it
What is the most common cause
Classical presentation
Ix/diagnosis
Congenital cause of primary adrenal insufficiency
Deficiency in enzymes involved in adrenal steroid synthesis pathways
-> 21-hydroxylase deficiency is most common cause (X-linked); salt wasting form
-> 11 beta hydroxylase deficiency is more rare
-> normal converts progresterone to aldosterone and cortisol precursor (get deficiency of these)
-> instead shunts it down androgen pathway so end up with EXCESSIVE androgen production)
Ix
- Decr cortisol and aldosterone
- Incr ACTH
- -> Cells in adrenal gland proliferate in compensatory response, resulting in adrenal gland hyperplasia and excess androgen precursors (testosterone +/- DHEA)
Sx -
21 hydroxylase deficiency: Presents in neonatal period
Signs of adrenal crisis (often in first 1-2 weeks)
- Salt wasting (hyponatraemia, hyperkalaemia, dehydration)
- GC deficiency (adrenal crisis; shock, hypoglycaemia)
- ACTH excess (hyperpigmentation)
Note: 11beta hydroxylase deficiency is characterised by incr levels of MC so get HTN and hyperNa and hypoK and adrenal crisis is much rarer
- Sx of androgen excess (both forms)
- -> Females: genital ambiguity (external masculinisation)
- Ambiguous genitalia (b/l undescended testes)
- Enlarged clitoris
- Early puberty
- Advanced bone age, tall stature
- Acne
- Hirsutism
- -> Males: *more likely to be diagnosed late *as appear normal at birth (may have hyper pigmented scrotum or enlarged phallus)
- dx often not made until signs of adrenal insufficiency in first 1-2 weeks (shock, dehydration, hypoNa, hyperK) or much later with precocious puberty/tall stature/adv bone age, skin pigmentation, HTN, hirsutism, acne
Ix
- NST
- Reduced levels of 21 hydroxylase, aldosterone, cortisol
- Increased levels of testosterone, androstenedione, ACTH, renin
- Elevated serum levels 17 hydroxyprogresterone (progest -> 17 hydroxyprogesterone -> 21 hydroxylase -> cortisol)
- HypoNa, HyperK, hypoglycaemia
Mx
- Hydrocortisone (synthetic cortisol) and fludrocortisone (synthetic aldosterone) daily
Cushing syndrome
Causes
Presentation
Endocrine disorder characterised by increased serum cortisol levels
Causes #1a Exogenous GC (medication) - most common #1b Pituitary adenoma ('cushings disease') secreting ACTH - most common -\> b/l adrenal hyperplasia #2 Adrenal adenoma/carcinoma producing excess cortisol #3 ectopic tissue excreting excess ACTH (neuroblastoma, Wilms) - v rare
Presentation
- Round, full moon shaped face
- Truncal obesity
- Skin thinning, striae, easy bruising
- Osteoporosis -> fractures
- Impaired growth -> short stature
- Muscle wasting, thin extremities
- Buffalo hump
- HTN
- Hyperglycaemia -> DM
- Decr immunity (incr infections particularly fungal)
- Menstrual irregularity
- Psychiatric disturbances
Investigation of cushing’s syndrome
- diagnosis and investigative pathway for aetiology
Step 1: Diagnosis
- Exclude iatrogenic (excess GC medication)
Need 2x neg results:
a) Late night (midnight) salivary cortisol test (should be low at midnight and high in morning; in cushings will be high at midnight)
Or
b) 24hr urinary free cortisol level (anything >3x ULN)
c) Overnight dex suppression test (low dose)
Step 2: underlying cause
Serum ACTH levels
a) If low = ACTH independent (ie cushings not due to excess ACTH, likely adrenal source)
b) If high = ACTH dependent (either pituitary adenoma=cushing disease or ectopic ACTH secretion ie not from pituitary)
Distinguish with HIGH DOSE dex suppression test (giving high dose dex should suppress ACTH release if coming from pituitary, but will not if coming from elsewhere)
–> If low = pituitary/cushing disease
–> if high (not suppressed) = ectopic ACTH secretion (not from pituitary)
OR can distinguish with the CRH stimulation test
- Administer IV CRH
- Measure serum ACTH and cortisol levels 45min post infection
–> Incr ACTH and cortisol = Cushing’s disease
–> No rise = ectopic ACTH secretion
If cushing’s disease confirmed:
-> MRI head to confirm location of pituitary adenoma
If ectopic ACTH secretion:
-> CT or MRI of CAP to determine tumour location, stage
If ACTH independent
- > Exclude iatrogenic GC
- > Abdo CT to identify ?adrenal mass
Features of benign vs malignant adrenal masses
More often benign adrenal adenoma
RF for malignant adrenal carcinoma:
- Age <10, >50
- Androgen excess in females (acne, deep voice, hirsutism)
CT: malignant more likely to have areas of haemorrhage, necrosis, calcification
Type 1 DM
- pathophys
- sx/presentation
- Ix
Pathophys:
Autoimmune pancreatic destruction (beta islet of langerhans cells)
- Often Ab against glutamic acid decarboxylase and Ab against islet cells (80% have ICA)
- Results in low insulin production -> glucose can’t be taken up into cells (‘starving in a sea of glucose’)
Sx appear when 90% of pancreatic islet cells have been destroyed:
- 2 peaks: 3-6yo; 10-14yo
- Presents with DKA
- Acute onset polyuria, polydipsia, polyphagia, glycosuria
- LOW
- Severe dehydration
- Abdo pain, N&V
- Ketotic (fruity) breath and kaussmal breathing
Ix
- Elevated GAD Ab
- Elevated IA2 Ab
- Decr C-peptide levels (reflects insulin deficiency)
Type 2 DM
- pathophys
- sx/presentation
- Ix
Insulin RESISTANCE
- Tissues aren’t taking up glucose despite normal insulin levels
- Beta cells of pancreas begin by producing more insulin to compensate -> eventually get ‘tired’ and beta cells die off -> then get decreased insulin production
RF
>45
Family hx
BMI > 25
Sedentary lifestyle
CV risk factors (HTN)
Presentation
- Polydipsia (secondary to dehydration)
- Polyuria (water follows excess glucose in urine)
- Polyphagia
- Unexplained LOW
Ix -
- Fasting glucose test
- OGTT
- Random glucose test
- HBA1c (% of glycated Hb in blood ie fraction of RBCs that have glucose stuck to them) > 6.5%
- incr c peptide levels (reflects high insulin leve;s_
Mx - basal bolus insulin
Chronic problems of DM
Persistent hyperglycaemia can damage
- vessels (arteriolosclerosis)
- nerves
- Diabetic retinopathy
- Diabetic nephropathy
- Peripheral and autonomic neuropathy
- Peripheral vascular disease
- > foot ulcers
Metformin
- Class
- MOA
- CI and S/E
Is a biguanide
Actions
- Increases insulin sensitivity and thus incr glucose uptake into tissues
- Promotes weight loss
- Doesn’t cause hypos
SE: nausea, diarrhoea, lactic acidosis
B12 deficiency -> macrocytic anaemia
CI: Chronic renal failure and heart failure (due to SE of lactic acidosis)
DKA
Causes
Presentation
Complications
Definition
1) Hyperglycaemia (and glycosuria)
-> BSL >11 (or fasting >7)
2) Metabolic Acidosis
-> pH <7.3 or bicarb <15
3) Ketonaemia (and ketonuria)
+/- high anion gap
Other ix
- HyperK initially -> risk of hypoK with insulin tx as K is pushed back into cells
- HypoNa
Causes
- First presentation T1DM
- Inadequate insulin
- Illness (incr insulin requirements)
Presentation:
- Dehydration
- Kussmaul respiration (deep, rapid breathing)
- Ketotic breathing (sweet and fuirty smelling)
- Abdo pain
- N&V
- Polyuria, polydipsia
- Mental status changes (delirium, psychosis, decr GCS) if cerebral oedema develops (hypoNa)
On first presentation do hypoglycaemia screen
Mgmt
Mild, tolerating oral intake:
- Give novorapid S/C (1unit/kg/day)
- Oral rehydration
- Recheck BSc, ketones 1 hr
Mod-severe:
- IV insulin infusion
- IV fluids (corrects dehydration)
- IV K if <5.5 (as insulin causes K uptake from blood into cells and can cause further hypokalaemia)
+/- IV bicarb if ph <7 or evidence of poor cardiac contractility
- regular monitoring of fluid balance, vitals, neuro obs, VBG/ketones, UEC (Na and K derangement), CMP (phosphate can drop)
Hypoglycaemia
Definition
Causes
- In DM-
- Non DM: transient vs persistent
BGL < 3.3 (<2.6 in infant)
Causes
In DM:
- Insulin (too much or not eating enough)
- Sulfonylureas
- Infection
- Too much exercise
Others:
Transient
- Prem, IUGR (decr liver glycogen and muscle protein and fat to use as substrate)
- Infant of diabetic mother (hyperinsulinism)
Persistent:
- Hyperinsulinism
- Insulinomas (insulin secreting tumours)
- Beckwith Wiedmann syndrome
- Persistent hyperinsulinaemic hypoglycaemia of infancy - Endocrine
- GH deficiency
- Hypopituitarism
- Adrenal insufficiency (ACTH, adrenaline deficiency, addison disease) - Substrate deficiency
- Eating disorder
- Ketotic hypoglycaemia (now ‘accelerated starvation’; essentially substrate decency) - METABOLIC
- Glycogen storage disorder
- Fatty acid oxidation defect
- Organic academia
- Carb metabolism disorder (galactosaemia, hereditary fructose intolerance, fructosaemia)
Sx (autonomic system activation)
- palpitations
- sweating
- shaking
- nausea
- hunger
- At extreme - confusion, seizure, coma
Mx
Give rapid oral glucose or soft drink/juice/milk feed followed by carb (bread or banana)
if comatose - give IV 10% dextrose 2ml/kg or IM glucagon
Features of diabetic retinopathy on fundoscopy
Cotton wool spots
Flare haemorrhages
Microaneurysms
Diabetic Nephropathy
Histological features
what is the earliest sign?
Nodular glomerulosclerosis
Histology:
Kimmelstiel-wilson nodules (clumps of hyaline material in arterioles)
Microalbuminaenuria is earliest sign -> can progress to CKD
Insulin tx in diabetes
- Long-acting insulin first, nocte (detemir or glargine)
-> adjust dose depending on morning fasting BSL - Add doses of rapid insulin throughout day, building to ‘basal bolus scheme’
= administer short-acting insulin 3 x day, before breakfast, lunch, dinner with nocte long-acting insulin
= measure BSL before each meal and before administering insulin
OR can give 2x doses pre-mix insulin/day (before breakfast and before dinner)
What do you give if cerebral oedema suspected in child w DKA
Mannitol (no NOT wait for CNS imaging, give immediately)
Causes of hypoglycaemia in the adolescent (non DM related)
Insulinoma
Adrenal insufficiency
eating disorder

