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

Cushing
syndrome

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 test

Cushings syndrome establised

Abnormal

 24h

urinary free cortisol

cortisol- 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 aetiologies
or 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 secretion

Bilateral 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

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

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 <120mmol/l, aim to correct by no more than 10mmol/l per 24h

 Hydrocortisone:

Bolus of 100mg hydrocortisone iv Hydrocortisone 100mg im continued 6- hourly for 24- 48h Double replacement doses (20- 30mg and 1020mg) Specific mineralocorticoid replacement is not required

 Without

treatment- invariably fatal, death occuring within 2 years after onset

autoimmune Addison survival approaches that of the normal population from adrenal insufficiency now occurs only in patients with rapid onset of disease (bilateral adrenal hemorrhage)

In

Death