Adrenal disorders

B O Gwer
 Introduction
• The adrenal glands are paired endocrine
organs consisting of cortex and medulla which
differ in development structure and function.
• The cortex is of mesodermal origin and is
involved in steroidogenesis.
• The medulla is of neuro-ectodermal origin
 Introduction
• The cortex consists of 3 zones:
- zona glomerulosa: is beneath capsule and primarily
produces mineralocorticoids
- zona fasciculata (75%) : is next and produces the
glococorticoids
- zona reticularis: next to medulla and produces mainly sex
steroids and a little glucocorticoids

• The adrenal medulla is composed of chromaffin cells that

secrete catecholamines mainly epinephrine but also
norepinephrine and dopamine
ADRENAL INSUFFICIENCY
 Introduction
• Primary Adrenal insufficiency: results from a
disease of the adrenal glands
• Secondary adrenal insufficiency: decreased
stimulation of adrenals owing to deficiency of
ACTH
• Causes may be in-born or acquired
Causes of adrenal primary insufficiency
• Auto-immune disease
• Infection:TB, CMV, HIV-1, fungal (cryptococus,
histoplasma, coccidiomycosis)
• Haemorrhage/infarction- meningococcal septic
shock (Waterhouse-Fredrichsen syn), primary
anti-phospholipid syndrome
• Infiltration: malignancy, amyloidosis
• Drugs: rifampicin, ketoconazole, suramin,
mifepristone
 Primary Causes cont
• Genetic disorders: Congenital Adrenal
Hyperplasia, Kearns-Sayre syndrome
• Surgical removal
 Secondary causes
• tumors (pituitary, craniopharyngioma, meningioma
etc)
• Inflammation (lymphocytic hypophysitis)
• Congenital ACTH def:pro-opiomelanocortin def
• Pituitary Infarcts: sheehans syndrome
• Infiltration/granulomatosis: TB, sarcoidosis
• Head injury
• Drugs: previous glucocorticoid excess for more than
4 weeks
 Clinical manifestations
• It depends on age of child and whether the extent
to which the deficiency affects the glucocorticoid
or mineralocorticoid axis.
• Infants have increased aldosterone requirement
so they prominently develop hyponatremia,
hyperkalemia on top of rapid hypoglycemia
• In infants the disease progression is rapid and
symptoms seen in older children may not be seen
 Clinicals
• In older children disease progression is
gradual with anorexia, myalgia, malaise,
vomiting, weight loss and orthostatic
hypotension
• They get ketosis, hypoglycemia, hyponatemia
and later hyperkalemia. Also hypercalcemia,
anemia lymphocytosis, eosinophilia and fever.
• Salt craving (hypoaldosterone) may occur
 Laboratory tests
• ACTH stimulation test:cortisol levels measured
before and after administration of ACTH is the
most definitive test, in primary disease the
levels do not increase significantly at time 0,
+30min, and + 60min
• Single cortisol levels may be low normal
• Early morning 9 am ACTH levels may be high
with low or low normal cortisol also confirms
disease.
 Laboratory tests
• Hypoglycemia, hypercalcemia, anemia
hyponatremia, hyperkalemia ketosis and
acidosis
• Adrenal antibodies in autoimmune disease
• Serum aldosterone usually reduced with high
renin
• Imaging tests to show cause eg TB. Calcified
adrenals in sarcoidosis, fibrosis
 Treatment
• Long-term replacement of glucocorticoids and
mineralocorticoid.
• Glucocorticoid:P O hydrocortisone 10-
15mg/m²/24hr in 3 divided doses
( prednisolone equivalent is 20-25% of this in
2 divided doses)- ACTH levels and clinical
well being used to monitor treatment
• During stress eg infection or surgery the doses
are increased 2-3 fold
 Treatment
• Aldosterone deficiency is corrected with
fludrocortisone and response monitored via renin
activity
• Chronic glucocorticoid over-dosage leads to short
stature, obesity and osteoporosis while
mineralocorticoid excess leads to tachycardia,
hypertension and hypokalemia
• Androgen replacement not usual in children but may
be used in adults
• Treat underlying cause eg TB
 Acute hypoadrenalism/crisis
• Acute disease requires urgent treatment
• Collect test samples before treatment
• Give 5% dextrose/0.9% saline for hypotension,
hypoglycemia and hyponatremia.
• If hyperkalemia is severe give Calcium
gluconate/bicarbonate, K binding resin and insulin/glucose
• IV hydrocortisone given 6 hourly over 1 st 24 hrs ( 10mg for
infants, 25- toddlers, 50-children and 100- adolescents)
• If co-existing hypothyroidism then treat adrenal insufficiency
1st as T3/T4 ppt cortisol clearance and cause crisis
 Secondary disease
• Aldosterone usually unaffected hence electrolytes
usually normal
• Neonates present with hypoglycemia while older
children have weakness and orthostatic hypotension
• Other signs of neurological disease eg optic signs may
be seen
• Treat only the glucocorticoid deficiency
• Iatrogenic disease avoided by use of minimum effective
steroid dose and if at risk taper down dose to dose
below physiologic replacement
CUSHING’S SYNDROME
 Introduction
• This is the clinical state arising from excess circulating
glucocorticoids.
• Most commonly iatrogenic due to excess synthetic
steroid administration.
• Endogenous excess as a result adrenal tumor or
excess ACTH also but rare
• In infants endogenous disease due to adrenal tumor
while in children > 7 yrs it is cushing disease with
pituitary micro-adenoma that may not be detectable
by imaging
 Causes
ACTH- dependent
• Pituitary excess ACTH
(Cushing’s disease)
• Ectopic ACTH producing
tumors
• Excess ACTH administration
Non-ACTH dependent
• Adrenal adenoma
• Adrenal carcinoma
• Excess exogenous
glucocorticoid
 Clinical manifestations
• Symptoms: obesity (general in infants but
truncal in older children), growth failure, thin
skin, moon facies, striae, ammenorhea,
oligomenorhea,, emotional changes with
depression and psychosis, polyuria and
polydypsia, muscle weakness
 Clinicals
• Signs: hirsutism, hypertension, proximal
muscle wasting, buffalo hump, glycosuria,
poor wound healing, sepsis risk, short stature,
osteoporosis with pathological fractures
 work-up
• Circadian rhythm: cortisol usually elevated at 8
am and lowest at midnight- maesuring over 48
hrs levels at 8 am and midnight this variation
lost in Cushing dz. Saliva may be used
• 24 hr urinary free cortisol
• A low -dose dexamethasone suppression test-
patients with cushing fail to suppress plasma or
urinary cortisol
 Work up
• Glucose tolerance test usually abnormal
• ACTH levels usually suppressed in adrenal
tumors and very high in ectopic ACTH tumors
• Administration of CRH show an exaggerated
ACTH and cortisol in ACTH dependent dz but no
response in adrenal dz.
• A high dose dexamethasone suppresion test
elicits a response (suppressed cortisol) in ACTH
dependent but not adrenal dz
 Work up
• CT scan: detects any adrenal tumor >1.5cm
diameter
• Brain MRI may detect pituitary tumors but
most too small for detection although contrast
enhancement with gadolinium improves
sensiltivity.
• Bilateral inferior petrosal blood sampling for
ACTH may help localise pituitary tumors
 Treatment
• Trans-sphenoidal pituitary micro-surgery is the
treatment of choice for pituitary Cushings
• Inhibitors (ketoconazole, metyrapone and
aminoglutethimide) used pre-op to normalise
levels before surgery
• If pituitary adenomas do not respond to surgery
then bilateral adrenalectomy done
• Benign adrenal adenomas treated with unilateral
adrenalectomy
 Treatment
• If benign adrenal tumors are bilateral then
sub-total bilateral adrenalectomy done with
good results
• Carcinomas usually metastasize to liver and
lungs so despite adrenalectomy resulys not
usually favorable
• Post-op hormone replacement usually
required(transient/permanent)
PRIMARY ALDOSTERONISM
• Very rare disorders of excess aldosterone
usually characterised by hypokalemia,
hypertension and suppresion of RAAS
• Etiology; usually caused by unilateral
adenomas common in younger children
usually girls and and bilateral micro-nodular
hyperplasia commoner in older children
usually boys.
 Clinicals
• Some have no symptoms except for incidental
findings of moderate hypertension
• Some present with severe high BP with
headache, dizziness and visual disturbances
• Chronic hypokalemia may lead to polyuria,
nocturia, polydypsia, tetany, muscle weakness,
growth failure fatigue and periodic paralysis.
 Lab findings
• Hypokalemia: a high salt diet given for several days
and diuretics stopped for 3 weeks.
• Urinary pottasium losses: levels of > 30mmol daily
despite hypokalemia is inappropriate
• Elevated plasma aldosterone levels not suppressed
with saline infusion or fludrocortisone.
• Suppressed plasma renin activity: avoid β blockers,
ACEIs, diuretics several weeks prior
• Adrenal CT or MRI to identify cause
 Treatment
• An adenoma is surgically removed
• Bilateral hyperplasia treated with aldosterone
antagonists – spironolactone, amiloride and
eplerenone + other anti-hypertensives if
neccesary.
• Unilateral adrenalectomy considered when
medical therapy fails.
PHAECHROMOCYTOMA
 Introduction
• Catecholamine producing tumors arising from
chromaffin cells.
• 90% arise in adrenal medulla while the rest in
sympathetic chain
• 20% of adrenal tumors are bilateral
• Some are associated with MEN syndrome
• A few may be malignant ( 10%)
• Commonest in children 6 – 14 yrs
 Clinical manifestations
Symptoms Signs
• Anxiety/panic attacks • Hypertension
• Palpitations/chest pain • Tachycardia/arrhythmia
• Tremor • Orthostatic hypotension
• Sweating and flushing • Pallor
• Headache
• Glycosuria
• Nausea , vomiting
• Fever
• Weight loss
• Constipation/diarrhea
• Papilloedema
• Raynauds • Htn encephalopathy
• Polyuria/nocturia
 Diagnosis
• Measurement of urinary catecholamines and
metabolites: metanephrine and VMA – are
raised
• Plasma metanephrine and VMA
• CT scans initially of abdomen to localise tumor
• MRI scans and ultrasound scans
• For extra-adrenal tumors 131-I meta-
iodobenzylguanidine scan has about 90% success
rate.
 Treatment
• Surgical removal if possible
• Medical pre-operative and peri-operative
treatment is vital especially β and α-
blockade as surgery is high risk
• If surgery not possible then combined α
and β-blockade in the long term