Lecture 20; Adrenal Gland Disease Flashcards
Can the adrenal glands be easily imaged?
No, very difficult
Two of them sit above the kidneys
How are the adrenal glands divided?
Into cortex and medulla regions
Describe what is produced where in the adrenal glands;
Cortex;
- Zona Glomerulosa = Mineral corticoids i.e Aldosterone
- Zona fasiculatis = Glucocorticois i.e cortisol
- Zona retigulcaris = androgens (imp. in women)
Medulla
- Adrenalin and noradrenalin
What are the functions of cortisol?
Stress hormone, energy metabolism, glucose homoeostasis
What do all adrenal cortex hormones originate from?
Cholesterol back bone precursor
Describe the adrenal cortex hormone production circuit;
Co-ordinated enzymatic steps (one goes wrong can be very bad)
What is the most common enzyme defect in the adrenal cortex pathway and whats the effects of this?
21-OH dysfunction
Shunts hormone production to the development of testosterone
- Inc. 17-hydroxyprogesterone (measure this as indicator)
- Decreased Aldosterone = Salt wasting and hyperkalemia
- Decreased Cortisol = Impaired response to stress and illness
- Increased testosterone = Virilization (in women)
Describe the HPA axis for cortisol production;
AVP and CRH in hypothalamus cause ACTH release from AP.
This results in cortisol release which negative feedbacks to hypothalamus and AP
What happens when there is excess secretion of glucocorticoids?
Cushings syndrome
- Moon face
- Obese
- hypertension
- mental abnormalities
Can be caused by;
- Adenoma
- Uncontrolled ACTH secretion
What happens in excess mineralcorticoid secretion?
Conn’s Syndrome
- Na retention
- Hypokalemia
- Hypoklameic alkalosis
What may cause deficient adrenal gland hormone secretion?
- Addinsons disease (hyperpigmentation, hypotension)
- Secondary adrenal insufficiency (usual due to steroid medicaiton)
- Adrenalectomy
Describe RAAS production of aldosterone;
- Decreased BP, BV, and osmolarity cause renin release —-> ANG 2 release
ANG2 acts on adrenal gland with ACTH = Aldosterone production
Aldosterone = increased K excretion and increase Na absortion = Increased BV and BP
Whats key to know in NE and EP production?
- Short lived in the circulation and are converted to stable metabolic products. (these can be measured for indirect values of EP and NE)
- EP -> Metanephrine
- NE -> Normetanephrine
What are the possible diseases when cortisol is in excess and insufficient?
Excess; Cushings syndrome
Insufficiency;
- Primary Adrenal failure, Addison’s disease
- Secondary Pituitary failure
What are the possible diseases when aldosterone is in excess and insufficient?
Excess; Primary hyperaldosteronism, hypertension and hypokalemia
Insufficiency; Adrenal failure, hypotension and ↑ sK+
What are the possible diseases when androgens are in excess and insufficient?
Excess; Virilization (women)
Insufficiency; No phenotype
What are the possible diseases when catecholamines are in excess and insufficient?
Excess; Pheochromocytoma, hypertension, paroxsymal symptoms
Insufficiency; No phenotype
What is the assessment for excess cortisol;
Excess; 24 hr urinary free cortisol, 1mg overnight dexamethasone suppression test
What is the assessment for insufficient cortisol;
Insufficiency
- Primary 1µg short synacthen test, basal ACTH
- Secondary 1µg short synacthen test
What is the assessment for excess aldosterone;
Excess; Plasma aldosterone to renin ratio
What is the assessment for insufficient aldosterone;
Insufficient; Renin (↑), aldosterone (↓), sK+ (↑)
What is the assessment for excess androgens?
Excess; Plasma testosterone (women)
- Basal and ACTH-stimulated 17(OH) progesterone (CAH)
What is the assessment for excess catecholamines?
Excess; Plasma metanephrines, 24 hr urinary metanephrines
What are the signs and symptoms of primary adrenal insufficiency?
- Fatigue, weakness
- Pigmentation of the skin and mucous membranes
- Bradycardia
- Dehydration
- Orthostatic hypotension
- Weight loss
- Loss of pubic hair
What are some blood markers of primary adrenal insufficiency?
Decreased cortisol response to ACTH,
Hypoglycemia
↑ sK+, ↓ sNa+, ↑ s creat
Test; 1µg short synacthen test
basal ACTH
What are the causes of primary adrenal insufficiency?
Autoimmune
Tuberculosis
Adrenoleukodystrohpy
Metastasis, hemorrhage
What exactly becomes hyperpigmented in addinsons disease?
Palmar creases
Buccal mucosa
How can primary and secondary adrenal insufficiency be differentiated?
Measuring plasma ACTH levels
- Primary = High 200+ units
- Secondary = normal, below 200
This is a compensatory mechanism in primary. Bi-product of high ACTH is MSH which causes the hyperpigmentation
What is the Synacthen test?
Synthetic ACTH is given and cortisol levels are measured.
<550nmol/L indicates there is a problem (primary) or secondary
What are some clinical clues as to the presense of primary aldosteronism?
- Spontaneous hypokalemia
- Diuretic induced hypoklamia
- Refractory Hypertension
- Family history
- Hypertension in young adults
What is another primary aldonesterism test?
Insulin tolerance test
What are the possible treatment options for adrenal insufficiency?
Glucocorticoid
- Hydrocortisone 15-25mg/day
- Increase dose for duration of minor illness
- HC 50-100mg tds for severe illness/major surgery
Mineralocorticoid (primary only)
- Fludrocortisone 0.1-0.2mg od
- Monitor renin and BP
- No change for illness
Androgens for women
MedicAlert bracelet!!
Describe the pathophysiolgy of primary hyperaldosteronism;
- Increased aldosterone secretion b/c
1) Aldosterone producing tumor (benign mostly)
2) Bilateral adrenal hyperplasia
=
- Increased BV, BP and hypokalemia
RAAS pathway decreases a lot (feedbacl) but no effect
What test can be done to detect primary hyperaldosteronism?
Screening plasma aldosterone to renin ratio (-ive feedback)
B/c high BP = Decreased Renin (glomerular feedback)
What tests can be done to diagnose primary hyperaldosteroism?
Potassium wasting (high in urine, low in serum) Suppressed plasma Renin Altered plasma renin;aldosterone ratio
Plasma aldosterone is on-supressible after salt loading
What is pheochromacytoma?
Cancer of the adrenal gland that results in excess catecholamines
How can pheochromacytoma be diagnosed?
Measure 24hr urine catecholamines (2-3x)
Urinary/serum fractioned metanephrines
CT/MRI
Whats the incidence of Adrenal Incidentaloma?
1-2% of abdominal CT scans 2-10% at autopsy Prevalence ↑ with age
(1-7% of AI are carcinoma)
even if known malignancy, >50% are benign
10% associated with cortisol autonomy 3% pheochromocytoma
1% aldosteronoma
How does a Adrenal Incidentaloma appear on the radiology?
Smooth, homogeneous favours adenoma
4cm
What is a Adrenal Incidentaloma density?
High fat content favours adenoma
< 2 HU unenhanced CT scan = benign [33% of AI]
Loss of signal on “out of phase” MRI favours adenoma
