64 ADRENAL GLAND ANATOMY AND PHYSIO.pptx

adrenal gland

1. ADRENAL GLANDS By Dr. RAJ SIDDARTHA

2. ANATOMY Situated on upper poles of kidneys, in the retroperitoneum, within Gerota’s capsule. Normal adrenal gland 4 gm. Components : the inner adrenal medulla the outer adrenal cortex

3. Right adrenal gland – between the right liver lobe and the diaphragm, close to and partly behind the inferior vena cava (IVC). 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. Arterial supply branches from - the aorta - the diaphragmatic artery - renal arteries . 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 αand 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. medulla synthesise - adrenaline (epinephrine) [major] - noradrenaline (norepinephrine) and dopamine. All necessary for the flight/fight response. Adrenal cortex secrets - Corticosteroids - Aldosterone - Cortisol

9. Zona glomerulosa : aldosterone - regulates sodium–potassium homeostasis. - target organs : kidneys, sweat and salivary glands, intestinal mucosa. - Promotes sodium retention and potassium excretion. - regulated by renin–angiotensin system , the serum potassium

10. Renin Angiotensin system Renin produced by the juxtaglomerular cells in kidneys Renin acts on angiotensinogen → Angiotensin I. Angiotensin converting enzyme (ACE) acts on Angiotensin I → angiotensin II. Angiotensinases convert angiotensin II → angiotensin III. 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. Adrenal disorders

15. INCIDENTALOMA An adrenal mass, - detected incidentally - by imaging done for other reasons - not previously present or causing symptoms. Prevalence – 1% patients - increases with age. More than 75% non-functioning adenomas

16. Rest -Cushing’s adenomas - phaeochromocytomas - metastases, - adrenocortical carcinomas - Conn’s tumours 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. 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). The sole indication for biopsy of an adrenal mass is to confirm a suspected metastasis from a distant primary site

19. 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

20. CONN’S SYNDROME (Primary hyperaldosteronism) Hypersecretion of aldosterone Plasma renin activity suppressed. Among patients with Incidence : 2% in patients with Hypertension. 12% of hypertensive - PHA with normal potassium levels

21. Cause of PHA with hypokalaemia - unilateral adrenocortical adenoma - 20–40% : bilateral micronodular hyperplasia - Rare : - bilateral macronodular hyperplasia - glucocorticoid-suppressible hyperaldosteronism - adrenocortical carcinoma. Mutations : KCNJ5 gene; codes potassium channel Kir3.4 are present adenomas Germline KCNJ5 mutation - autosomal dominant, early-onset PHA.

22. CLINICAL FEATURES Age 30 and 50 years Female predominance. Hypertension Headache Muscle weakness Cramps Polyuria, polydypsia and Nocturia.

23. DIAGNOSIS Biochemical - aldosterone to plasma renin activity ratio. - Hypokalaemia may be present. MRI or CT - unilateral or bilateral disease. - CT sensitivity of 80–90% 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 Bilateral hyperplasia – spironolactone -supplemental antihypertensive medication to control blood pressure. Unilateral or asymmetrical bilateral disease - laparoscopic adrenalectomy Subtotal adrenal resection - typical single Conn’s adenoma

25. CUSHING’S SYNDROME Hypersecretion of cortisol. Most common cause pituitary adenoma secreting ACTH. 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 – elevated - loss of diurnal rhythm. Dexamethasone fails to suppress 24-hour urinary cortisol excretion. Elevated or normal ACTH - ACTH-producing pituitary tumour (85%) - ectopic ACTH production Elevated ACTH - MRI of the pituitary gland MRI if negative - venous sampling from the inferior petrosal sinus

28. CT chest and abdomen for ectopic ACTH-producing tumour. Suppressed ACTH levels - CT or MRI to assess adrenals. Subclinical Cushing’s 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 - ectopic ACTH-dependent Cushing’s - 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. Nelson’s 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. In selected circumstances an adrenalectomy is appropriate

33. ADRENOCORTICAL CARCINOMA Incidence: 1–2 cases per 1000 000/ year Slight female predominance (1.5:1). Age distribution – 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. Macroscopic features - multinodularity - heterogeneous structure - haemorrhage and necrosis

35. CLINICAL FEATURES About 60% - Cushing’s syndrome. 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

36. DIAGNOSIS Biochemistry : DHEAS - cortisol and catecholamines - dexamethasone suppression test. Imaging : MRI and CT (equally effective) - MRI angiography - exclude tumour thrombus in IVC - preoperative staging CT

37. World Health Organization classification - <5cm - stage I - >5 cm - stage II - locally invasive – stage III - Distant metastases – stage IV

38. TREATMENT Complete tumour resection (R0) - favourable survival capsule must not be damaged - prevents tumour spillage and implantation metastases Local spread - En bloc resection + removal of involved organs is often Tumour thrombus in IVC - thrombectomy needed Tumour debulking - functioning tumours.

39. Postoperatively - mitotane alone - combination with etoposide, doxorubicin and cisplatin. Adjuvant radiotherapy - reduce the rate of local recurrence. After surgery, restaging every 3 months -risk of relapse is high. Prognosis - stage of disease - complete removal of tumour. Stage I or II : 5-year survival rate of 25% Stage III : 5-year survival rate of 6% stage IV : 0%

40. CONGENITAL ADRENAL HYPERPLASIA (adrenogenital syndrome) Pathognomonic - Virilisation - adrenal insufficiency Autosomal recessive disorder. Enzymatic defects in cortisol, other steroids synthesis. Most frequent defect (95%) : 21-hydroxylase deficiency Loss of cortisol Excessive ACTH release increase in androgenic cortisol precursors and to CAH.

41. Presentation - at birth with ambiguous genitalia - late-onset disease at puberty. Hypertension Short stature - premature epiphyseal plate closure. Treatment : replace cortisol - fludrocortisone. 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. Secondary adrenal insufficiency - deficient ACTH. Tertiary adrenal deficiency - loss of hypothalamic CRH caused by - therapeutic glucocorticoid administration - brain tumour, trauma or irradiation

43. ACUTE ADRENAL INSUFFICIENCY Presents as shock - fever - nausea, vomiting - abdominal pain, - hypoglycaemia - electrolyte imbalance. Waterhouse – Friderichsen syndrome - bilateral adrenal infarction associated with meningococcal sepsis

44. CHRONIC ADRENAL INSUFFICIENCY Symptoms develop over time -anorexia -weakness and nausea. ACTH and pro-opiomelanocortin (POMC) levels increase - hyperpigmentation of the skin and oral mucosa. - Hypotension - hyponatraemia - hyperkalaemia - hypoglycaemia

45. Diagnosis - ACTH stimulation test. - Basal ACTH levels high - cortisol levels decreased. Synacthen test - the exogenous administration of ACTH - no rise in cortisol levels

46. TREATMENT Treatment – immediate, before awaiting biochemical diagnosis. Intravenous hydrocortisone 100 mg every 6 hours 3 litres of saline is given in 6 hours withcardiovascular monitoring. Concomitant infections - antibiotics. Chronic adrenal insufficiency - daily oral hydrocortisone 10 mg/m 2 body surface - fludrocortisone (0.1 mg).

47. ADRENAL MEDULLA AND NEURAL CREST DERIVED TISSUE

48. PHAEOCHROMOCYTOMA AND PARAGANGLIOMA Tumours of the adrenal medulla and sympathetic ganglia Produce excess of catecholamines. Aetiology Prevalence in patients with hypertension - 0.1–0.6% overall prevalence 0.05% in autopsy series. 4% of incidentalomas

49. Sporadic phaeochromocytomas - fourth decade Hereditary forms younger age. Phaeochromocytoma- ‘10% tumour’ - 10% of tumours are inherited - 10% are extra-adrenal - 10% are malignant - 10% are bilateral - 10% occur in children.

50. Hereditary phaeochromocytomas (syndromic) Multiple endocrine neoplasia type 2 (MEN 2): - autosomal dominant - activating germline mutations of the RET proto-oncogene. 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. Von Hippel–Lindau (VHL) syndrome: - early-onset bilateral kidney tumours - phaeochromocytomas - cerebellar and spinal haemangioblastomas - pancreatic tumours - germline mutation in the VHL gene. Neurofibromatosis (NF) type 1: - Phaeochromocytomas - fibromas on the skin and mucosae :‘café-au-lait’ spots - germline mutation in the NF1 gene

52. PATHOLOGY Cut surface : greyish-pink Highly vascularised. Areas of haemorrhage or necrosis 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. In MEN 2, phaeochromocytoma is preceded by adrenomedullary hyperplasia, sometimes bilateral. Phaeochromocytoma is rarely malignant in MEN 2

55. CLINICAL FEATURES Symptoms and signs typically intermittent.

56. Patients with the combination of -headache -palpitations -sweating -presence of an adrenal tumour have a phaeochromocytoma. Paroxysms precipitated by - physical training - induction of general anaesthesia - drugs and agents (contrast media, tricyclic antidepressive drugs, metoclopramide and opiates).

57. Hypertension may be – continuous - intermittent - absent. More than 25% sporadic phaeochromocytomas due to germline mutations in RET, SDHB, SDHC, SDHD and NF1 genes;

58. DIAGNOSIS First step - confirmation of excessive catecholamine levels by 1) measurement metanephrine and normetanephrine in 12 or 24-hour urine collection - 2–40 times normal value 2) Plasma-free metanephrine and normetanephrine levels. Second step - localisation of the phaeochromocytoma. - MRI preferred

59. MRI - ‘Swiss cheese’ configuration 123 I-MIBG ( metaiodobenzylguanidine ) single-photon emission computed tomography (SPECT) - identify about 90% of primary tumours - used for multiple extra-adrenal tumours and metastases. Positron emission tomography (PET) scanning using fluorodeoxyglucose (FDG) or dihydroxyphenylalanine (DOPA) - more sensitive in detecting metastatic foci.

60. TREATMENT Laparoscopic resection Open surgery - If tumour is larger than 8–10cm - radiological signs of malignancy

61. PREOPERATIVE Α adrenoreceptor blocker (phenoxybenzamine) to block catecholamine excess - 20mg of phenoxybenzamine - increased daily by 10mg - final dose 100–160mg Additional β-blockade if tachycardia or arrhythmias

62. A central venous catheter and invasive arterial monitoring are used. Infusion of large volumes of fluid or use of noradrenaline to correct postoperative hypotension in the presence of unopposed α-blockade

63. Observe 24 hours for – hypovolaemia - hypoglycaemia Lifelong yearly biochemical tests to - identify recurrent - metastatic - metachronous phaeochromocytoma

64. MALIGNANT PHAEOCHROMOCYTOMA Approximately 10% are malignant. - higher in extra-adrenal tumours (paragangliomas). There’s 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 - α-blockers.

65. Mitotane - adjuvant or palliative treatment. 5-year survival rate of less than 50%. PHAEOCHROMOCYTOMA IN PREGNANCY Silent and present as a hypertensive emergency - may mimic an amnion infectionsyndrome or - pre-eclampsia. α-blockade prevents hypertensive crisis during delivery.

66. First and second - laparoscopic adrenalectomy - after adequate α-blockade; Risk of a miscarriage during surgery - high. Third trimester - elective caesarean with delayed consecutive adrenalectomy 6 weeks Maternal mortality is 50% if phaeochromocytoma undiagnosed

67. NEUROBLASTOMA Neuroblastoma malignant tumour of sympathetic nervous system - adrenal medulla (38%) - along the sympathetic chain abdomen (30%), - chest (20%) - rarely neck or pelvis.

68. PATHOLOGY Pale and grey surface Encapsulated and show areas with calcification. Necrosis and haemorrhage may be detected. Immature cells from the neuroectoderm of the sympathetic nervous system. Mature cells - ganglioneuroblastomas

69. CLINICAL FEATURES Predominantly newborn infants and young children (<5 years) 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.

70. DIAGNOSIS Biochemical - urinary excretion (24-hour urine) of -vanillylmandelic acid (VMA) - homovanillic acid (HVA), - dopamine - noradrenaline Increased levels - 80% of patients.

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. Patients are classified as low, intermediate or high risk. Low-risk - surgery alone Intermediate-risk - surgery with adjuvant multiagent chemotherapy. High-risk patients - high-dose multiagent chemotherapy followed by surgical resection in responding tumours.

73. GANGLIONEUROMA Benign neoplasm from neural crest tissue In the adrenal medulla - mature sympathetic ganglion cells - Schwann cells in a fibrous stroma. CLINICAL FEATURES More common before the age of 60. Occur along the paravertebral sympathetic plexus, adrenal medulla (30%).

74. INVESTIGATION Identified incidentally by CT or MRI done for other indications. TREATMENT Treatment is by surgical excision, laparoscopic when adrenalectomy is indicated

75. SURGERY OF THE ADRENAL GLANDS Laparoscopic or retroperitoneoscopic adrenalectomy - ‘gold standard’ (except if signs of malignancy) Advantage of retroperitoneoscopic approach - minimal dissection. In the case of small, bilateral tumours or in patients with hereditary tumour syndromes - subtotal An open approach should be considered if suggestive of malignancy.

76. Principles of surgery Knowledge of the anatomy of the adrenal region is essential. Careful haemostasis is essential To prevent tumour spillage, direct grasping of the adrenal tissue/tumour has to be avoided.

77. Right adrenalectomy Position - right side up. Three ports placed Dissection starts at the level of the periadrenal fat Peritoneum – divided 2 cm below the edge of the liver from medial (IVC) to the lateral abdominal wall . Liver retracted up The gland is identified and mobilised The vein is secured with a clip The gland is removed in a plastic catch bag

78. Left adrenalectomy Position: left side up Mobilisation of the spleen medially Incision of Gerota’s fascia , identification of the adrenal vein, running into the renal vein Resection by mobilising the adrenal gland at the level of the periadrenal fat. Remove the gland in a bag.

79. Retroperitoneoscopic adrenalectomy Position : prone . 1 st port – distal end of 1 st rib Digital dissection into the retroperitoneum Gerota’s fascia is displaced ventrally. Right side vein: covered by the retrocaval posterior aspect of the adrenal gland. Left side vein : medial inferior pole of the adrenal gland. High inflation pressures - effectively tamponading the veins.

80. Open adrenalectomy Performed - malignant adrenal tumour is suspected. Hepatic flexure of the colon is mobilised and the right liver lobe is cranially retracted On the left side mobilisation of the splenic flexure of the colon The remaining dissection is the same as in laparoscopic adrenalectomy. Resection of regional lymph nodes recommended in malignant tumours.

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