2. ANATOMY
â˘Situated on upper poles of kidneys, in the retroperitoneum,
within Gerotaâs capsule.
â˘Normal adrenal gland 4 gm.
â˘Components : the inner adrenal medulla
the outer adrenal cortex
3. â˘Right adrenal gland
â between the right liver
lobe and the diaphragm, close to
and partly behind the inferior
vena cava (IVC).
â˘Left adrenal gland
- close to the upper pole of
the left kidney and the renal
pedicle.
- covered by the pancreatic
tail and the spleen
4. â˘Arterial supply branches from
- the aorta
- the diaphragmatic artery
- renal arteries .
â˘Venous drainage - single large adrenal vein
- on the right side into the vena cava
- on the left side into the renal vein.
5. EMBRYOLOGY
The two functional parts
⢠Cortex - mesodermal cells
⢠Medulla - neuroectodermal cells
from the neural crest
6. HISTOLOGY
⢠Outer zona glomerulosa
- small, compact cells.
⢠Central zona fasciculata
- larger, lipoid-rich cells,
- arranged in radial columns.
⢠Inner zona reticularis
- Compact and pigmented cells
⢠Medulla
- thin layer of large chromaffin cells
7. FUNCTIONS
⢠Pivotal role in the response to stress.
⢠Adrenal medulla : Catecholamines
- effects mediated through ιand β adrenergic receptors
- Effects : cardiovascular system
- increase in blood pressure and heart rate
- vasoconstriction of vessels in the splanchnic system
- vasodilatation of vessels in the muscles
- bronchodilatation
- increased glycogenolysis in liver and muscles
8. â˘medulla synthesise
- adrenaline (epinephrine) [major]
- noradrenaline (norepinephrine) and dopamine.
⢠All necessary for the flight/fight response.
â˘Adrenal cortex secrets
- Corticosteroids
- Aldosterone
- Cortisol
9. â˘Zona glomerulosa : aldosterone
- regulates sodiumâpotassium homeostasis.
- target organs : kidneys, sweat and salivary glands,
intestinal mucosa.
- Promotes sodium retention and potassium excretion.
- regulated by reninâangiotensin system , the serum
potassium
10. Renin Angiotensin system
â˘Renin produced by the juxtaglomerular cells in kidneys
â˘Renin acts on angiotensinogen â Angiotensin I.
â˘Angiotensin converting enzyme (ACE) acts on Angiotensin I â
angiotensin II.
⢠Angiotensinases convert angiotensin II â angiotensin III.
â˘Angiotensin II, III
- secretion of aldosterone from the adrenal cortex.
- in response to decrease renal blood flow or
hyponatraemia
11. Decrease renal blood flow or hyponatraemia
renin secretion
Sodium retention, potassium excretion
increase of plasma volume.
12. ⢠Zona fasciculata and zona reticularis
- synthesise cortisol
- adrenal androgens dehydroepiandrosterone(DHEA)
dehydroepiandrosterone sulphate DHEAS.
⢠DHEA and DHEAS - precursors of androgens
- converted in peripheral tissues such as fat.
⢠Cortisol secretion regulation
Hypothalamus: corticotrophin-releasing hormone(CRH)
anterior pituitary gland : adrenocorticotrophic hormone (ACTH)
Adrenal cortex: cortisol
13. ⢠Cortisol
- increases gluconeogenesis and lipolysis
- decreases peripheral glucose utilization
- inhibits immunological response
-reduces muscular mass
- affects fat distribution
wound healing
bone mineralisation
- alters mood (euphoria or, rarely, depression)
- alters brain cortical activity and alertness.
14.
15. INCIDENTALOMA
â˘An adrenal mass,
- detected incidentally
- by imaging done for other reasons
- not previously present or causing symptoms.
⢠Prevalence â 1% patients
- increases with age.
â˘More than 75% non-functioning adenomas
16. â˘Rest -Cushingâs adenomas
- phaeochromocytomas
- metastases,
- adrenocortical carcinomas
- Connâs tumours
â˘Diagnosis: exclude a functioning or malignant adrenal tumour.
- complete history and clinical examination
- biochemical work-up for hormone excess
- imaging studies
17. ⢠Hormonal evaluation includes:
- morning and midnight plasma cortisol measurements
- a 1-mg overnight dexamethasone suppression test
- 24-hour urinary cortisol excretion;
- 12- or 24-hour urinary excretion of metanephrines or
plasma-free metanephrines;
- serum potassium
- plasma aldosterone and plasma renin activity;
- serum DHEAS, testosterone or 17-hydroxyestradiol
18. â˘Imaging, in all patients with adrenal masses
- CT or MRI.
⢠The chance of an adrenal mass being carcinoma increases
with size of the mass (25% >4 cm).
â˘The sole indication for biopsy of an adrenal mass is to confirm
a suspected metastasis from a distant primary site
19. â˘Treatment
- non-functioning tumour >4 cm or increase in size over
time surgical resection.
- Non-functioning tumours <4 cm follow-up after 6, 12 and
24 months by imaging (MRI) and hormonal evaluation.
- non-functioning, stable in size, surveillance discontinued
22. CLINICAL FEATURES
â˘Age 30 and 50 years
â˘Female predominance.
â˘Hypertension
â˘Headache
â˘Muscle weakness
â˘Cramps
â˘Polyuria, polydypsia and
â˘Nocturia.
23. DIAGNOSIS
â˘Biochemical - aldosterone to plasma renin activity ratio.
- Hypokalaemia may be present.
â˘MRI or CT - unilateral or bilateral disease.
- CT sensitivity of 80â90%
â˘Selective adrenal vein catheterisation :
- decide on non-surgical or surgical treatment
- samples from the vena cava and from both adrenal veins
- aldosterone to cortisol ratio (ACR) determined in each
24. TREATMENT
â˘Bilateral hyperplasia â spironolactone
-supplemental antihypertensive medication to
control blood pressure.
â˘Unilateral or asymmetrical bilateral disease
- laparoscopic adrenalectomy
â˘Subtotal adrenal resection - typical single Connâs adenoma
25. CUSHINGâS SYNDROME
â˘Hypersecretion of cortisol.
â˘Most common cause pituitary adenoma secretingACTH.
â˘Ectopic ACTH-producing tumours
- small cell lung cancer
- foregut carcinoid
- CRH-producing tumours - medullary thyroid carcinoma
-neuroendocrine pancreatic tumour
26. Clinical features
⢠Central obesity, due to fat redistribution
⢠Puffy face, moon face
⢠Proximal muscle wasting
⢠Hyperglycemia
27. DIAGNOSIS
⢠Morning and midnight plasma cortisol levels â elevated
- loss of diurnal rhythm.
⢠Dexamethasone fails to suppress 24-hour urinary cortisol
excretion.
⢠Elevated or normal ACTH - ACTH-producing pituitary tumour (85%)
- ectopicACTH production
⢠Elevated ACTH - MRI of the pituitary gland
⢠MRI if negative - venous sampling from the inferior petrosal sinus
28. â˘CT chest and abdomen for ectopicACTH-producing tumour.
â˘Suppressed ACTH levels - CT or MRI to assess adrenals.
â˘SubclinicalCushingâs syndrome
- clinical symptoms - absent
- abnormal cortisol secretion
29. TREATMENT
⢠Medical - metyrapone or ketoconazole - reduces steroid synthesis
and secretion
- can be used preoperatively
- if surgery is not possible.
⢠ACTH-producing pituitary tumours - trans-sphenoidal resection
- radiotherapy
⢠Ectopic ACTH - resection of source.
⢠Unilateral adenoma - adrenalectomy.
⢠Bilateral adrenalectomy - ectopicACTH-dependent Cushingâs
- irresectable or unlocalised primary
30. PREOPERATIVE
⢠Prophylactic anticoagulation, prophylactic antibiotics are essential.
⢠Control Diabetes, hypertension.
POSTOPERATIVE MANAGEMENT
⢠After unilateral adrenalectomy - supplemental cortisol
- 15mg/h IV for first 12 hours
- daily dose of 100mg for 3 days
- gradually reduced thereafter.After unilateral
⢠Synacthen test to evaluate adrenal function before stopping
cortisol supplements
31. ⢠Nelsonâs syndrome
- in bilateral adrenalectomy after failed pituitary surgery
- ACTH secretion at high levels
- causes hyperpigmentation
- due to synergies between ACTH melanocyte-stimulating
hormone
32. ADRENAL METASTASES
Most common primary tumours
-breast
- lung
- renal
- gastric
- pancreatic
- ovarian
- colorectal cancer.
â˘In selected circumstances an adrenalectomy is appropriate
33. ADRENOCORTICAL CARCINOMA
â˘Incidence: 1â2 cases per 1000 000/ year
â˘Slight female predominance (1.5:1).
â˘Age distribution â bimodal
- first peak in childhood
- second peak fourth and fifth decades.
34. PATHOLOGY
Criteria for malignancy
- tumour size
- presence of necrosis or haemorrhage
- microscopic features - capsular or vascular invasion.
â˘Macroscopic features - multinodularity
- heterogeneous structure
- haemorrhage and necrosis
35. CLINICAL FEATURES
â˘About 60% - Cushingâs syndrome.
â˘Non-functioning tumours - abdominal discomfort
- back pain ( large tumours)
- incidental finding.
⢠Adrenal tumours secreting more than one hormone in excess
- feminising/masculanising steroids
- likely to be malignant
38. TREATMENT
â˘Complete tumour resection (R0) - favourable survival
â˘capsule must not be damaged - prevents tumour spillage and
implantation metastases
â˘Local spread - En bloc resection + removal of involved organs
is often
â˘Tumour thrombus in IVC - thrombectomy needed
â˘Tumour debulking - functioning tumours.
39. â˘Postoperatively - mitotane alone
- combination with etoposide, doxorubicin and
cisplatin.
â˘Adjuvant radiotherapy - reduce the rate of local recurrence.
â˘After surgery, restaging every 3 months -risk of relapse is high.
â˘Prognosis - stage of disease
- complete removal of tumour.
â˘Stage I or II : 5-year survival rate of 25%
â˘Stage III : 5-year survival rate of 6%
â˘stage IV : 0%
40. CONGENITAL ADRENAL HYPERPLASIA
(adrenogenital syndrome)
â˘Pathognomonic - Virilisation
- adrenal insufficiency
â˘Autosomal recessive disorder.
â˘Enzymatic defects in cortisol, other steroids synthesis.
â˘Most frequent defect (95%) : 21-hydroxylase deficiency
â˘Loss of cortisol
â˘ExcessiveACTH release
â˘increase in androgenic cortisol precursors and to CAH.
41. Presentation - at birth with ambiguous genitalia
- late-onset disease at puberty.
â˘Hypertension
â˘Short stature - premature epiphyseal plate closure.
â˘Treatment : replace cortisol
- fludrocortisone.
â˘Large hyperplastic adrenals - removed if symptomatic
42. Adrenal insufficiency
⢠Primary adrenal insufficiency - loss of function of adrenal
cortex.
- Symptoms seen when 90% of the adrenal cortex is
destroyed.
â˘Secondary adrenal insufficiency - deficientACTH.
⢠Tertiary adrenal deficiency - loss of hypothalamicCRH
â˘caused by - therapeutic glucocorticoid administration
- brain tumour, trauma or irradiation
44. CHRONIC ADRENAL INSUFFICIENCY
â˘Symptoms develop over time
-anorexia
-weakness and nausea.
â˘ACTH and pro-opiomelanocortin (POMC) levels increase
- hyperpigmentation of the skin and oral mucosa.
- Hypotension
- hyponatraemia
- hyperkalaemia
- hypoglycaemia
45. â˘Diagnosis - ACTH stimulation test.
- Basal ACTH levels high
- cortisol levels decreased.
â˘Synacthen test - the exogenous administration of ACTH
- no rise in cortisol levels
46. TREATMENT
â˘Treatment â immediate, before awaiting biochemical
diagnosis.
⢠Intravenous hydrocortisone 100 mg every 6 hours
⢠3 litres of saline is given in 6 hours withcardiovascular
monitoring.
â˘Concomitant infections - antibiotics.
â˘Chronic adrenal insufficiency
- daily oral hydrocortisone 10 mg/m2 body surface
- fludrocortisone (0.1 mg).
47.
48. PHAEOCHROMOCYTOMA AND PARAGANGLIOMA
â˘Tumours of the adrenal medulla and sympathetic ganglia
â˘Produce excess of catecholamines.
Aetiology
â˘Prevalence in patients with hypertension - 0.1â0.6%
â˘overall prevalence 0.05% in autopsy series.
⢠4% of incidentalomas
49. â˘Sporadic phaeochromocytomas - fourth decade
â˘Hereditary forms younger age.
â˘Phaeochromocytoma- â10% tumourâ
- 10% of tumours are inherited
- 10% are extra-adrenal
- 10% are malignant
- 10% are bilateral
- 10% occur in children.
50. â˘Hereditary phaeochromocytomas (syndromic)
⢠Multiple endocrine neoplasia type 2 (MEN 2):
- autosomal dominant
- activating germline mutations of the RET proto-
oncogene.
â˘Familial paraganglioma (PG) syndrome:
- glomus tumour of the carotid body
- extra-adrenal paraganglioma
- germline mutations of succinate dehydrogenase complex
subunit B (SDHB) SDHD and SDHC genes.
51. â˘Von HippelâLindau (VHL) syndrome:
- early-onset bilateral kidney tumours
- phaeochromocytomas
- cerebellar and spinal haemangioblastomas
- pancreatic tumours
- germline mutation in theVHL gene.
â˘Neurofibromatosis (NF) type 1:
- Phaeochromocytomas
- fibromas on the skin and mucosae :âcafĂŠ-au-laitâ spots
- germline mutation in the NF1 gene
52. PATHOLOGY
â˘Cut surface : greyish-pink
â˘Highly vascularised.
â˘Areas of haemorrhage or
necrosis
â˘Microscopically : tumour cells
- polygonal.
53. ⢠Differentiation between malignant and benign tumours is difficult
- Increased PASS (phaeochromocytoma of the adrenal gland
scale score)
- High number of Ki-67-positive cells
- vascular invasion or a breached capsule
⢠Phaeochromocytomas may also produce
- calcitonin
- ACTH
- vasoactive intestinal polypeptide (VIP)
- parathyroid hormone-related protein (PTHrP).
54. â˘In MEN 2, phaeochromocytoma is preceded by
adrenomedullary hyperplasia, sometimes bilateral.
â˘Phaeochromocytoma is rarely malignant in MEN 2
56. â˘Patients with the combination of
-headache
-palpitations
-sweating
-presence of an adrenal tumour
have a phaeochromocytoma.
â˘Paroxysms precipitated by - physical training
- induction of general anaesthesia
- drugs and agents (contrast media, tricyclic
antidepressive drugs, metoclopramide and opiates).
57. â˘Hypertension may be â continuous
- intermittent
- absent.
â˘More than 25% sporadic phaeochromocytomas due to
germline mutations in RET, SDHB, SDHC, SDHD and NF1
genes;
58. DIAGNOSIS
â˘First step - confirmation of excessive catecholamine levels by
1) measurement metanephrine and normetanephrine
in 12 or 24-hour urine collection
- 2â40 times normal value
2) Plasma-free metanephrine and normetanephrine
levels.
â˘Second step - localisation of the phaeochromocytoma.
- MRI preferred
59. ⢠MRI - âSwiss cheeseâ configuration
â˘123I-MIBG (metaiodobenzylguanidine) single-photon emission
computed tomography (SPECT) - identify about 90% of
primary tumours
- used for multiple extra-adrenal tumours and
metastases.
â˘Positron emission tomography (PET) scanning using
fluorodeoxyglucose (FDG) or dihydroxyphenylalanine (DOPA) -
more sensitive in detecting metastatic foci.
61. PREOPERATIVE
â˘Î adrenoreceptor blocker (phenoxybenzamine) to block
catecholamine excess
- 20mg of phenoxybenzamine
- increased daily by 10mg
- final dose 100â160mg
â˘Additional β-blockade if tachycardia or arrhythmias
62. â˘A central venous catheter and invasive arterial monitoring are
used.
â˘Infusion of large volumes of fluid or use of noradrenaline to
correct postoperative hypotension in the presence of
unopposed Îą-blockade
64. MALIGNANT PHAEOCHROMOCYTOMA
⢠Approximately 10% are malignant.
- higher in extra-adrenal tumours (paragangliomas).
⢠Thereâs metastases of chromaffin tissue, most commonly to lymph
nodes, bone and liver.
TREATMENT
⢠Surgical excision
⢠Metastatic disease - tumour debulking ( to control the
catecholamine excess)
⢠Symptomatic treatment - ι-blockers.
65. â˘Mitotane - adjuvant or palliative treatment.
â˘5-year survival rate of less than 50%.
PHAEOCHROMOCYTOMA IN PREGNANCY
â˘Silent and present as a hypertensive emergency
- may mimic an amnion infectionsyndrome or
- pre-eclampsia.
â˘Îą-blockade prevents hypertensive crisis during delivery.
66. â˘First and second - laparoscopic adrenalectomy
- after adequate Îą-blockade;
â˘Risk of a miscarriage during surgery - high.
â˘Third trimester - elective caesarean with delayed consecutive
adrenalectomy 6 weeks
â˘Maternal mortality is 50% if phaeochromocytoma undiagnosed
68. PATHOLOGY
â˘Pale and grey surface
â˘Encapsulated and show areas with calcification.
â˘Necrosis and haemorrhage may be detected.
â˘Immature cells from the neuroectoderm of the sympathetic
nervous system.
â˘Mature cells - ganglioneuroblastomas
69. CLINICAL FEATURES
â˘Predominantly newborn infants and young children (<5 years)
â˘Present with - a mass in abdomen, neck or chest
- proptosis
- bone pain
- painless bluish skin metastases
- weakness or paralysis.
⢠Metastatic 70% of patients at presentation.
71. ⢠Staging as per International Neuroblastoma Staging System
(INSS)
⢠Staging needs
- CT/MRI of the chest and abdomen
- a bone scan,
-bone marrow aspiration
- core biopsies
- MIBG scan.
72. ⢠Prognosis - tumour stage
- age at diagnosis.
â˘Patients are classified as low, intermediate or high risk.
â˘Low-risk - surgery alone
â˘Intermediate-risk - surgery with adjuvant multiagent
chemotherapy.
â˘High-risk patients - high-dose multiagent chemotherapy
followed by surgical resection in responding tumours.
73. GANGLIONEUROMA
â˘Benign neoplasm from neural crest tissue
â˘In the adrenal medulla - mature sympathetic ganglion cells
- Schwann cells in a fibrous stroma.
CLINICAL FEATURES
â˘More common before the age of 60.
â˘Occur along the paravertebral sympathetic plexus, adrenal
medulla (30%).
74. INVESTIGATION
â˘Identified incidentally by CT or MRI done for other indications.
TREATMENT
â˘Treatment is by surgical excision, laparoscopic when
adrenalectomy is indicated
75. SURGERY OFTHE ADRENAL GLANDS
â˘Laparoscopic or retroperitoneoscopic adrenalectomy - âgold
standardâ (except if signs of malignancy)
â˘Advantage of retroperitoneoscopic approach - minimal
dissection.
â˘In the case of small, bilateral tumours or in patients with
hereditary tumour syndromes - subtotal
â˘An open approach should be considered if suggestive of
malignancy.
76. Principles of surgery
â˘Knowledge of the anatomy of the adrenal region is essential.
â˘Careful haemostasis is essential
â˘To prevent tumour spillage, direct grasping of the adrenal
tissue/tumour has to be avoided.
77. Right adrenalectomy
â˘Position - right side up.Three ports placed
â˘Dissection starts at the level of the periadrenal fat
â˘Peritoneum â divided 2 cm below the edge of the liver from
medial (IVC) to the lateral abdominal wall.
â˘Liver retracted up
â˘The gland is identified and mobilised
â˘The vein is secured with a clip
â˘The gland is removed in a plastic catch bag
78. Left adrenalectomy
â˘Position: left side up
â˘Mobilisation of the spleen medially
â˘Incision of Gerotaâs fascia , identification of the adrenal vein,
running into the renal vein
â˘Resection by mobilising the adrenal gland at the level of the
periadrenal fat.
â˘Remove the gland in a bag.
79. Retroperitoneoscopic adrenalectomy
â˘Position : prone. 1st port â distal end of 1st rib
â˘Digital dissection into the retroperitoneum
â˘Gerotaâs fascia is displaced ventrally.
â˘Right side vein: covered by the retrocaval posterior aspect of
the adrenal gland.
â˘Left side vein : medial inferior pole of the adrenal gland.
â˘High inflation pressures - effectively tamponading the veins.
80. Open adrenalectomy
â˘Performed - malignant adrenal tumour is suspected.
â˘Hepatic flexure of the colon is mobilised and the right liver lobe
is cranially retracted
â˘On the left side mobilisation of the splenic flexure of the colon
â˘The remaining dissection is the same as in laparoscopic
adrenalectomy.
⢠Resection of regional lymph nodes recommended in malignant
tumours.