Adrenal Gland

the adrenal gland is made up of the outer cortex & inner medulla 

arterial supply comes from the inferior mesenteric artery & renal arteries as well as the aorta

venous drainage of the L is via the L renal vein but the R drains directly into the IVC

CORTEX

3 x Layers of the Adrenal Cortex. (go find rex, make good sex)

LAYER	STEROID	CONTROL
Zona Glomerulosa	Mineralocorticoids (aldosterone)	Renin-Ang II controls
Zona Fasciculata (80% of cortex)	Glucocorticoids (cortisol)	ACTH (circadian, stress, -ve feedback)
Zona Reticulata	Sex hormones (DHEAs)	ACTH

MEDULLA

• is the principal site of the conversion of the amino acid tyrosine into the catecholamines; epinephrine, norepinephrine, and dopamine. 
• In response to stressors, such as exercise or imminent danger, medullary cells release the catecholamines adrenaline and noradrenaline into the blood.
• Clinical significance
  • Neoplasms include:
    • Pheochromocytoma (most common), a catecholamine-secreting tumor of the adrenal medulla
    • Neuroblastoma, a neuroendocrine tumor of any neural crest tissue of the sympathetic nervous system

Glucocorticoids – Cortisol

Actions:

• CHO metabolism
  • ↑ BGL by stimulation of glycogenolysis & gluconeogenesis 
• Protein metabolism
  • ↑ breakdown with overall negative nitrogen balance
• Fat metabolism
  • Selective lipolysis – loss of body fat in the limbs but ↑ accumulation over the lower face & trunk 
• Anti-inflammatory
  • Reduced synthesis of PGs & LTs, sequestration of Nφ & Eφ
• Endocrine
  • Suppression of pituitary hormones  (GLAPT)

Effects of excess (Cushing’s syndrome)

• hyperglycaemia
  • from stimulation of glycogenolysis & gluconeogenesis
• negative N balance with protein loss
  • osteoporosis, muscle wasting (esp. proximally), ↓ fibroblasts – thin skin, easy bruising, plethoric face (also due to ↑ RBC production)
• salt & water retention
  • tendency to CHF (HTN)
  • associated hypokalaemia (due to Na retention & subsequent K loss)
• immunosuppression
• abnormal fat metabolism 
• moon face, cervical fat pad, central obesity but thin arms/legs (lemon on a stick)

• suppression of ACTH secretion (negative feedback)
• neutrophilia (because Nφ & lymphocytes are kept in the blood to stop activation of immune response)
• mental effects (depression & confusion, can get euphoria & psychosis too)

Effect of deficiency:

• ↑ sensitivity to insulin – tendency to hypoglycaemia 
• ↓ mobilisation of peripheral fat & protein
• ↓ gluconeogenesis
• Inability to excrete a water load
• Loss of salt & water: hyponatraemia & hyperkalaemia 
• ↓ Na & ↑ K
• Loss of negative feedback suppression of ACTH
• Non-specific malaise, fatigue & GI upset

Mineralocorticoids – Aldosterone

Actions:

• Na+, K+ & H+ balance 
• Na+ & H2O retention with loss of K+ & H+ as a result
• Mineralocorticoids also have weak glucocorticoid activity 

Effects of excess:

• salt & water retention with loss of K+ & H+ 
• causes HTN & hypokalaemic alkalosis 

Effects of deficiency: 

• salt & water deficiency – volume depletion with postural hypotension 
• also associated hyperkalaemia & mild metabolic acidosis 
• in practice, aldosterone deficiency is almost always associated with glucocorticoid deficiency (Addison’s disease) 

Sex steroids – Dehydroepiandrosterone 

– the adrenal cortex secretes both androgens & oestrogens in both men & women

– adrenals secrete testosterone in small amounts but mainly make weak androgens like dehydroepiandrosterone sulphate (DHEAs) & androstenedione

Effect of excess: 

• Androgens:
  • Excess androgen may be seen in women & children but not in adult men
  • Two causes: androgen-secreting tumours & congenital adrenal hyperplasia 
  • Women get acne, hirsutism, balding, ↑ muscle bulk, clitoromegaly, virilism (deepening of voice) 
  • Boys/girls – false puberty growth spurt, ‘pseudopuberty’ & clitoromegaly 
• Oestrogens:
  • Main effect of oestrogen excess in men is gynaecomastia 
  • In premenopausal women it is menstrual disturbance with breakthrough bleeding

Effect of deficiency:

• There are none if gonadal function in intact
• Children with Addison’s disease go through a normal puberty 

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Initial investigations of adrenal disease
Adrenal disease	Initial investigation(s)
Adrenal incidentaloma	Dedicated adrenal CT scan to differentiate benign from malignant lesionTo assess functionality, screen for Cushing’s syndrome, primary aldosteronism and phaeochromocytoma (see below)
Cushing’s syndrome	1 mg overnight dexamethasone suppression test, orMidnight salivary cortisol (measured twice), or24-hour urinary free cortisol (measured twice)
Primary aldosteronism	Aldosterone-to-renin ratio
Phaeochromocytoma	Plasma metanephrines, or24-hour urinary metanephrines
Adrenal insufficiency	Early morning cortisol and ACTH

Causes of adrenal masses

Adenoma Carcinoma Phaeochromocytoma Congenital adrenal hyperplasia Massive macronodular adrenal disease Nodular variant of Cushing’s syndrome Myelolipoma Neuroblastoma Ganglioneuroma Haemangioma Lymphoma Metastasic malignancy Cyst Haemorrhage Amyloidosis Infiltrative and granulomatous diseases including tuberculosis

Adrenal incidentaloma: A disease of imaging

• An adrenal incidentaloma is defined as an adrenal mass lesion >1 cm in diameter that is serendipitously discovered by radiological examination, in the absence of symptoms or clinical findings suggestive of adrenal disease
• key question is whether the lesion is benign or malignant
• 3–10% of the population have adrenal tumours
• Incidence increases with age
• adrenal carcinoma occurs in <2 cases per million per year
• A benign lesion may be functionally active:
  • adrenal cortex synthesising cortisol and aldosterone
  • adrenal medulla produces catecholamines. 
  • Clinically this may be reflected in symptoms and signs of Cushing’s syndrome, primary aldosteronism (PA) or phaeochromocytoma respectively
• however, in the context of an incidentaloma, the features are, by definition, subtle or occult. 
• Hypertension should provoke further investigation
  • Phaeochromocytoma
    • plasma metanephrine levels are very sensitive and a normal value in this context can be taken to exclude a phaeochromocytoma (which is also ruled out if the lesion is ≤10 HU).
  • Primary aldosteronism:
    • serum potassium test is useful but not sensitive
    • aldosterone
    • renin and their ratio are the optimal screening tests
  • Cushing’s syndrome
    • overnight dexamethasone suppression test