B1: RMcC Adrenal Gland Flashcards
Embryological origin od adrenal gland, when does it form?
Neuroectodermal cells - medulla
Mesenchyma - cortex
Adrenal Glands present in fetuses ~2months development
Basic anatomy of adult adrenal gland
3-4cm wide, ~1cm thick, 4-6g
Located on superior poles of kidneys
Blood supply from suprarenal / adrenal branches from abdominal aorta
Zones of Medulla/Cortex
Cortex = 80%
- Outer Capsule
- Zona Glomerulosa (15%)
- Zona Fasciculata (75%)
- Zona Reticularis
Medulla = 20%
Hormones secreted, by area:
All hormones synthesized and secreted by cortex are derived from choelsterol*
Zona Glomerulosa = Aldosterone
Zona Fasciculata = Cortisol
Cona Reticularis = Androgens & Estrogens
Medulla = Epinepherine and Nor-epinephrine
Normal feedback loop - cortisol
Hypothalamus -> secretion of CRH
Anterior Pituitary -> Secretion of ACTH
-> Adrenal Cortex (zona fasciculats) -> Cortisol
Cortisol then feeds back to inhibit secretion of both CRH and ACTH
How is cortisol circulated, and when does it carry out its action?
Secreted unbond
Travels in plasma, bound to plasme proteins
Active form = unbound
Actions of Cortisol:
- Decreased immune responses
- Bone reabsorption and decreased bone formation
- Decreased connective tissue
- Increased muscle function and decreased muscle mass
- Wakefulness
- Modulation of emotional tone
- Increased glomerular filtration and free water excretion
- Supports CO and peripheral tone
- Facilitates fetal maturation
Describe how the SNS acts on the body - including the adrenal gland (general terms)
Various structures feed input into Hypothalamus, which feeds into the brainstem (ANS centres) and SC
Sympathetic nerves -> Sympathetic Ganglia -> Postganglionics -> NA/A onto specific innervated tissues
Alternatively: Postganglionic axons release ACh onto Adrenal Medulla -> release of Epinephrine / Norepinephrine into blood circulation -> systemic effect
Epidemiology of Adrenal Insufficiency
Prevalence: 40-110/1,000,000
F:M ratio = 2.6:1
Usually diagnosed in 3rd-5th decades
Primary Adrenal Insuffciency - Causes
Autoimmune Adrenalitis -> 70% of cases
Other causes:
- haemorrhagic adrenal damage (coagulopathies, heparin)
- Infective causes (HIV, TB, Histoplasmosis)
- Polyglandular autoimmune 2
- Adenoleukodystrophy
- APECED
Secondary Adrenal INsufficiency - what is it, and causes
Adrenal ‘insufficiency’ that is secondary to problems ‘upstream’ -> results in low corticoid release
- Glucocorticoid Use -> HPA Axis Suppression
(Dexamethasone most prominantly does this, followed by Fludrocortisone, Prednisolone, Methylprednisolone, then cortisol itself) - Anterior Pituitary Problems:
e. g. Pituitary Adenomas, Haemorrhage affecting pituitary, Metastatic Malignancy - Developmental Abnormalities
Clinical Features of Adrenal Insufficiency:
Skin: - Increased pigmentation of face, palms, areas subject to friction, skin folds, scars, freckling, dair darkening, mucous membranes, nipples - Decreased skin pigmentation Weakness Weight loss, emaciation Anorexia, Diarrhoea, Vomiting Salt Cravings Hypotension Hypoglycemic Episodes
Diagnosing Adrenal Insufficiency:
Can be done with ‘Endocrine Stimulation Test’
*want to isolate primary adrenal insufficiency as cause -> not due to secondary causes
Give synthetic ACTH 250mcg IV Normal Response (measured free cortisol) @ 0 mins - cortisol - 220mmol/L @ 30 mins -------------550 @ 60 mins -------------550
If cortisol fails to rise in response to synthetic ACTH, then it is adrenal insufficiency
How can we test for secondary or tertiary abnormalities associated with decreased cortisol levels?
Metyrapone Testing
Describe Metyrapone Testing:
Tests for 2ndary or 3iary abnormalities assoc. w/ low cortisol
Metyrapone prevents cortisol synthesis by inhibiting the 11B-deoxycortisol conversion to cortisol
Premise: giving metyrapone will prevent cortisol production, which should therefore result in both increased 11B-deoxycortisol AND ACTH
Steroid-induced HPA axis suppression: in order of most HPA-suppressing to least so
Dexomethasone - most Fludrocortisone (most salt retention) Prednisolone Methylprednisolone Cortisol - least
Problems with metyrapone testing?
Can induce adrenal crisis
Requires: fluid rescusitation (saline + sucrose)
And 100mg IV bolus hydrocortisone + Q6hr 100mg IV
Aldosterone - where is it produced and what does it do in the body?
Produced by Zona Glomerulosa of Adrenal Cortex
Acts on Distal Tubules of the Nephron, resulting in:
- Increased Na+ reabsorption
- (and thus increased water reabsorption)
- Increased K+ loss in urine
What is Hyperaldosteronism - signs
Over-production of Aldosterone
(Believed to account for a significant proportion of mod-severe HTN)
Signs:
- HTN (often resistent)
- Hypokalaemia
- High serum aldosterone
- loe serum renin (*remember ald feeds back to suppress renin in the RAS)
Primary Causes of Hyperaldosteronism
- Bilateral Idiopathic Adrenal Hypertrophy
- Adrenal Adenoma (Adenomatous Primary Aldosteronism)
(Rarer causes: congenital adrenal hyperplasia; adrenal carcinoma)
Secondary causes of Hyperaldosteronism
Usually due to overactivity of the RAS, which can be due to:
- Juxtaglomerular cell tumour (produces renin -> stimulates RAS)
- Renal artery stenosis (reduced flow to juxtaglomerular cells -> stimulates RAS)
Overview of RAS
Decreased flow to juxtaglomerular cells -> Releases Renin
Renin converts Angiotensinogen to Angiotensin I
ACE converts Angiotensin I to Angiotensin II
Angiotensin II (and angiotensin III) causes release of Aldosterone
Aldosterone acts on distal nephron (increased Na+ and H2O reabsorption and increased K+ loss)
Aldosterone feeds back to suppress Renin activity
Coming to a diagnosis for primary hyperaldosteronism: i.e. differentiating between adenoma and bilateral hyperplasia
Patient Presents with: Resistant HTN and Unprovoked Hypokalaemia
Test Aldosterone-Renin-Ratio (ARR) -> if normal, excluse primary hyperaldosteronism as cause
Is ratio is high -> want to re-test after making some adjustments
Adjustments:
- Normalize serum K+ levels
- Adequate Na+ intake
- Cease BP medication if possible
- Repeat ARR
- Conduct 24hr urine aldosterone
If repeated ARR normal -> excluse PA as cause
If ratio still high, conduct ADRENAL CT SCAN
On scan:
- If micronodules Medical Treatment -> Diagnosis = Bilateral Adrenal Hyperplasia
- If still suspicous of adenoma, can do Adrenal Venous Sampling, to check for lateralization. Lateralization indicates Adenomatous Primary Aldosteronism. No lateralization = Bilateral Adrenal Hyperplasia
- If mass(es) >1cm are present:
- > and patient is >40 years old, conduct AVS to check for lateralization.
- > If patient <40 years old…
Treatment is Unilateral Adenalectomy
As diagnosis is Adenomatous Primary Aldosteronism
What is Cushing’s Syndrome:
A collection of clinical features (signs and symptoms) associated with chronically elevated cortisol
