Lecture 9
Oct 31, 2014
Lecture 9
Located
above the kidneys, small, averaging 35cm in lengh.
They
are made of 2 different components derived from 2 distinct embriological origins: the cortex and the medula.
They
play an important role:
in the regulation of the bodys adaptative response to stress In the maintenance of body water and salt balance In the control of blood presure
The
main hormones produced by the human adrenal glands are:
The steroid hormone CORTIZOL The mineralocorticoid ALDOSTERONE The androgen DEHIDROEPIANDROSTERONE The catecolamines: EPINEPHRINE NOREPINEPHRINE
and
ACTH
dependent
Pituitary adenoma (Cushings disease) Nonpituitary neoplasm (ectopic ACTH- small cell carcinoma of the lung) Ectopic CRH secretion
ACTH
independent
Iatrogenic (glucocorticoid) Adrenal neoplasm (adenoma, carcinoma) Nodular adrenal hyperplasia Factitious
Diverse
symptom complex resulting from:
excess steroid hormone production by the adrenal cortex (endogenous) Sustained administration (exogenous) of glucocorticoids
Obesity:
Especially central (truncal obesity) With wasting of the extremities Moon facies (plethoric facies) Supraclavicular fat pads Buffalo hump
Skin
changes:
Atrophy of the epidermis and conective tissuethinning of the skin and facial plethora Easy bruisability following minimum trauma Striae usuallt red to purple, depressed below the skin surface; most commonly abdominal, on breasts, hips, thighs and axillae Acne- hyperandrogenism Poor wound healing hyperpigmentation
Psychologic
disturbances:
Emotional lability Increased irritability Anxiety Depression Poor concentration and poor memory
Cardiovascular
manifestations:
Hypertension Congestive heart failure
Menstrual Low
disturbance
libido and impotence
Hirsutism
Facial hirsutism- most common
Growth
arrest in children
Less
common features:
Impaired glucose tolerance/ diabetus mellitus Osteopenia and osteoporosis Vascular disease Susceptibility to infections
11pm salivary cortisol Disrupted circadian rhythm
Cushingsyndrome
24hour urine free cortizol Increased filtered load of cortizol Low- dose dexamethasone suppression test Attenuated negative feedback
suspected
Normal If test above
Cushings syndrome excluded Repeat if high index of suspicion
Equivocal
Dexamethasone CRH testCushings syndrome establised
Abnormal
24h
urinary free cortisolcortisol- in Cushing syndrome it is
Midnight
elevated Overnight
dexamethasone suppresion test:
Administration of 1mg Dexamethasone at midnight followed by serum cortisol measurement at 9a.m.
Low
dose dexametasone suppression test (2x2):
Administration of 0,5mg dexamethasone 6-hourly for 48h Interpretation: normal subjects show suppression of serum cortisol
High
dose dexamethasone suppression test (2x8):Administration of 2mg dexamethasone 6-hourly for 48h Interpretation: more than a 50% reduction in plasma cortisol- pituitary Cushing
Plasma
ACTH: used to differentiate between ACTH dependent and ACTH independent aetiologiesor pituitary Cushing- basal levels of ACTH are mesurable
Ectopic
Adrenal
Cushing syndrome- undetectable levels of ACTH
CRH
stimulation test
Interpretation: ACTH and cortisol levels increase in 90% in patients with pituitary Cushing
The
8mg overnight dexamethasone suppression test can be used in place of the 2-day dexamethasone suppression test
Interpretation: more than a 50% reduction in plasma cortisol- pituitary Cushing
Other
tests:
Urinary 17- hydroxycorticosteriods (17-OHCS)
Adrenal
Cushing syndrome:
CT scan of the adrenal- one or more lessions can be seen, uni- or bilateral MRI complements the CT
Pituitary
Cushing:pituitary ACTHsecreting
MRI detects a microadenoma
Ectopic
Cushing syndrome:
Full lung CT and MRI scans
Inferior
petrosal sinus sampling- the most reliable means of distinguishing pitutary from nonpitutary ACTH hypersecretion
Obesity Alcoholic
hypercorticism Untreated diabetes Chronic use of glucocorticoids Severe depression Hypercorticism due to stress, puberty or pregnancy
1.
Cushings disease:
Transsfenoidal adenectomy or hypophysectomy is the treatment of choice
Postoperative hypoadrenalism is expected
Pituitary x-irradiation
Medical therapy to block cortisol secretionBilateral adrenalectomy
Drawbacks
in bilateral adrenalectomy:
Adrenal insufficiency and dependence onn exogenous glucocorticoids and mineralocorticoids Nelsons syndrome- in 30% of patients after adrenalectomy an aggressive corticotrop pituitary toumor appears
2.
Cushings Syndrome (adrenal):adrenal adenomasremoved by
Unilateral surgery
Adrenal carcinoma- surgery If inoperable carcinoma- medical treatment with MITOTANE (adrenolytic agent) Ketoconazole, metyrapone, aminoglutethimide can be used
3.
Ectopic Cushing syndrome:
Mitotane Metyrapone Aminoglutethimide Ketoconazole
Untreated Treated
is fatal in more than 50%
Cushings syndrome has a good
prognosis Physical
features improve or resolve within weeks or months
Disorders of adrenocortical insufficiency
Defficient
adrenal production glucocorticods or mineralocorticoids
of
The
manifestations of insufficeincy do not appear until at least 90% of the galnd is destryed
Autoimune Infiltration:
most common (~70%)
Amyloid Haemocromatosis Tuberulosis Fungal (histoplasmosis) Opportunistic infections mycobacterium)
Infection:
(AIDS,
CMV,
Malignancy:
Metastatic (lung, breast, kidney) lymphoma
Vascular
haemorrhage (adrenal) Infarction Adrenoleucodystrophy Congenital adrenal hyperplasia Familial glucocrticoid deficiency hypoplasia Iatrogenic:
and
Adrenalectomy Drugs: ketoconazole, metyrapone, aminoglutethimide, mitotane, etomidane
Manifestations
are gradual in onset
Mineralocorticoid
deficiency leads to reduced SODIUM retention and HYPOTENSION and HYPERKALEMIA Lack of cortisol:
Negative feedback increases CRH and ACTH secretion
Androgen
deficiency:
In female: reduced axillary and pubic hair and reduced libido
Symptoms:
Weakness- generalized, fatigue, tiredness Anorexia GI symptoms- nausea and vomiting, abdominal pain, diarhoea or constipation Depresion, psychosis Dizziness and postural hypotension Arthralgia and myalgia Loss of axillary and pubic hair and reduced libido Salt craving
Signs:
Weight loss (>90%) Hyperpigmentation- generalized Associated with vitiligo or other autoimmune endocrinopathies Pyrexia of unknown origin- rare
Hyperpigmentation:
generalized, but more
common:
In light exposed areas In areas exposed to pressure (elbows and kness) Mucosae and scars Palmar creases
Serum
cortisol:
Low Sometimes normal in basal conditions
ACTH-
elevated PRA is increased Hyponatremia
(90%) Hyperkalemia (65%) Hypogligemia
Short
Synacten test (syntethic ACTH):
Inject 250g ACTH i.v. Obtain repeat samples of serum cortisol 30 and 60 min after Failure to respond adrenal failure (cortisol should rise to 580nmol/L)
Long
Synacten test:
Inject depot ACTH 1mg Measure serum cortisol at 30, 60, 120 min. and 4, 8, 12, 24h after administration No response in primary adrenal failure
Abdominal
radiographs- calcifications patients with tuberculous Addison radiographs- tuberculosis lesions
in
Toracic
Abdominal
CT- adrenal calcifications and adrenal inlargement
A
state of acute adrenocortical insufficiency
Occurs:
In patients with Adissons disease who are exposed to stress (infection, trauma, surgery, dehydratation) Adrenal hemorrhage Prolonged corticotherapy
Clinical
features:
Hypotension, shock Fever (due to infection) Dehydratation, volume depletion Nausea, vomiting, anorexia Abdominal pain (may mimic acute abdomen) Weakness, apathy, depressed mentation Hypoglycemia
Investigations:
As chronic- plasma cortizol, ACTH Hyponatremia Hyperkalemia Eosinophilia Hypoglicemia
Differential
diagnosis:
Acute abdominal emergency Hypoglicemic coma Hepatic coma
Glucocorticoid
replacement:
Hydrocortisone is the tratement of choice: 1015mg in the morning and 5-10 mg in the afternoon Prednisolone 5- 7,5mg on waiking and 2,5- 5mg in the afternoon Cortisone acetate 25mg in the morning and 12,5mg in the afternoon
Mineralocorticoid
replacement:
Fludrocortisone 100mcg daily; occasionlly lower or higher doses are required
Adrrenal
androgen replacement (DHEA and
DHEAS):
May improve overall sense of well- being and mood
Monitoring
of therapy:
For signs of hypercorticism- exces in weight gain; hypertension Hypertension and oedema suggest excessive mineralocorticoid replacement Salt craving and postural hypotensioninsufficient treatment
Intercurent
illness or steress:
Minor illness (respiratory tract infection; dental extraction)- double dosage Major stress:
20mg hydrocortisone orally or 100mg i.v. before surgery 50- 100mg im/iv hydrocortisone 6- hourly for 2-3 days
Patient
edducation:
Instruction to adjust glucocorticoid dosage for mild ilnesses and stressful events Allways cary a card or wear a bracelet indicating they steriod dependency A traveling kit that provides hydrocortisone, dexamethasone, cortisone acetate for iv/ im injection
Patient
education
Normal or increased salt intake
A
life- threatening emergency
Blood
taken for urgent analysis (cortisol, ACTH, electrolytes, glucose)
Fluids:
Large volumes of 0,9% saline- several liters in 2448h If plasma Na