By;Col Abrar Zaidi

1. ADRENAL MEDULLASURGICAL CONDITIONS CLINICAL FEATURES INVESTIGATIONS MANAGEMENT By;Col Abrar Zaidi

2. SEQUENCE • INTRODUCTION • SURGICAL CONDITIONS

3. INTRODUCTION It is an overview with stress on certain important surgical aspects

4. INTRODUCTION Surgical importance why study this subject again ? • Not an uncommon occurrence • All ages and both genders • Retroperitoneal masses • Incidental finding • Vague symptoms/diagnostic challenge

5. INTRODUCTIONSURGICAL ANATOMY-ADRENALS • The adrenal glands are bilateral, endocrine glands located near the upper pole of each kidney • Each weighs 3–5 g and is bright yellow in color. • Vascular supply- Numerous small arteries from the inferior phrenic artery, the aorta, and the renal artery. • The right adrenal vein enters the posterior aspect of the vena cava; the left adrenal vein enters the left renal vein. • Two main parts – cortex and medulla

6. INTRODUCTIONSURGICAL ANATOMY-ADRENALS

7. INTRODUCTIONSURGICAL ANATOMY-ADRENALS • Adrenal Cortex • Adrenal Medulla

8. INTRODUCTIONSURGICAL ANATOMY-ADRENALS

9. INTRODUCTIONSURGICAL ANATOMY-ADRENALS ADRENAL CORTEX There are three cortical zones: • Zona glomerulosa, (aldosterone), • Zona fasciculata (cortisol). • Zona reticularis (sex steroids),

10. INTRODUCTIONSURGICAL ANATOMY-ADRENALS ADRENAL MEDULLA • Extremely vascular • consists largely of a reticular network of catecholamine-secreting chromaffin cells with • Closely related plexus of venous sinusoids . This facilitates release of catecholamines into the circulation. • Rich nerve supply derived mainly from the coeliac and renal plexuses. The nerve endings terminate directly on the chromaffin cells • synthesis and storage of catecholamines. adrenaline +smaller quantities of noradrenaline . • Release - in flash of seconds

11. INTRODUCTIONSURGICAL ANATOMY-ADRENALS ECTOPIC ADRENAL TISSUE The incidence of extra-adrenal medullarytissue is very high compared to the incidence of extra-adrenal cortical tissue Functioning extra-adrenal medullary tissue occurs in about 1 in 8 cases of medullary hyperfunction, it occurs in fewer than 1 in 1000 cases of adrenocortical hyperfunction.

12. INTRODUCTIONPHYSIOLOGY-ADRENAL MEDULLA The sympatho-adrenal system consists of: 1- A sympathetic- neuronal component that uses norepinephrine as the main neurotransmitter and 2- Adreno-medullary secretory hormone, epinephrine, the main hormone secreted into the bloodstream. The system influences; cardiovascular, metabolic, and visceral activity, and its typical effects are observed during severe stress. Release of norepinephrine at sympathetic nerve endings is critical for maintenance of normal blood pressure, especially during upright posture. Epinephrine metabolites (e.g., nor-meta-nephrine, meta-nephrine, and VMA) are excreted with catecholamines in the urine.

13. INTRODUCTION SPECTRUM OF ADRENALS FUNCTIONS • PITUTARY ADRENAL AXIS [ACTH] • RENO-ADRENAL CONNECTION [Aldos] • SYMPATHATIC CONNECTION [ Coeliac & renal plexuses con. With chromaffin cells]

14. INTRODUCTIONFUNCTIONS OF ADRENALS • METABOLISM & IMMUNE RESPONSE human stress response • FLUID & ELECTROLYTES • VASCULAR VOLUME,BLOOD PRESSURE • SEXUAL FUNCTION

15. SURGICAL CONDITIONS

16. SURGICAL PATHOLOGYADRENAL MEDULLA • Hypofunction Developmental /Acquired Agenesis,Anaplasia/ Hypoplasia • Hyperfuction • Mass Effects

17. SURGICAL PATHOLOGYADRENAL MEDULLA Loss of Medulary tissue – • Fulminant infections • Tumour invasion /compression

18. SURGICAL PATHOLOGYADRENAL MEDULLA MEDULLARY-HYPERFUNCTION Clinical conditions • Increased catecholamines action • Adrenal medullary tumours/masses Adenoma carcinoma

19. SURGICAL PATHOLOGYADRENAL MEDULLA ADRENAL TUMOURS PRIMARY VS SECODARIES BENIGN VS MALIGNANT

20. SURGICAL PATHOLOGYADRENAL MEDULLA ADRENAL TUMOURS- FACTS • INCIDENTELOMAS- 0.6 percent of abdominal USG or CT scans • Most are usually benign, nonfunctional adenomas (autopsy incidence 10 percent). • Careful history and physical examination • Determinations of the 24-h urine for free cortisol level (Cushing's syndrome), vanillylmandelic acid (VMA), and catecholamines (pheochromocytoma). • Aldosterone and renin should be measured in any patient with hypertension or hypokalemia. • A mass larger than 5 cm may be carcinoma and should be resected. • Smaller masses should be remeasured by CT in 6 months and resected if larger or left alone if unchanged. • If pheochromocytoma is excluded and metastatic disease is suspected, a fine-needle aspiration (FNA) may be helpful .

21. SURGICAL PATHOLOGYADRENAL MEDULLA TUMOURS OF THE ADRENAL MEDULLA A-Neoplasms of the sympathetic neurons:      1-Ganglioneuroma,     2-Neuroblastoma (sympatheticoblastoma) B-Neoplasm of chromaffin cells: Phaeochromocytoma.  NEURONAL TUMOURS –CHROMAFFIN TUMOURS

22. SURGICAL PATHOLOGYADRENAL MEDULLA Clinical presentation in general • An unsuspected tumor that is found on a CT scan performed for another reason:As CT scan evaluation of the abdomen has become widespread, an unsuspected swelling of the adrenal gland is frequently detected in many patients. These tumors should be carefully evaluated. • Production of symptoms due to over secretion of hormones from the tumor: The adrenal gland may produce distinct syndromes based on the profile of the hormones that are secreted by the tumor.

23. GANGLIONEUROMA Tumours occurring at any age • A relatively benign. • Symptom less • Grows to a large size • A type of retroperitoneal sarcoma • Only15 per cent involve the adrenal • Most occur in other position along the sympathetic chain. • cured If removed early

24. NEUROBLASTOMA Tumours occurring in infants and children • Malignant tumour of neural crest origin • Arise from sympathetic nervous tissue from the orbit to the pelvis. • Three-quarters arise in the abdomen and half of these from the adrenal gland. • The most common solid tumour of infancy and childhood, and the most common in the newborn. • The incidence is approximately 1 per 10 000 live births. • Ninety per cent of cases of neuroblastoma occur under the age of 8; over half occur in children under 2 years.

25. NEUROBLASTOMA - CLINICAL FEATURES • An abdominal mass - pain and distension Three-quarters of patients • Metastatic spread: via lymphatics and bloodstream, occurs at an early stage, and approximately 70 per cent of cases have metastases at the time of initial diagnosis . • Weight loss, failure to thrive, • Fever and anaemia may be present. • Hypertension, flushing, general irritability sweating Excessive catecholamine production, and. • watery diarrhoea and hypokalaemia -some tumours produce VIP, which results in. • Acute cerebellar ataxia characterised by opsomyoclonus and chaotic nystagmus or the ‘dancing eye syndrome is an unusual manifestation of neuroblastoma of unknown cause.

26. NEUROBLASTOMA CLINICAL FEATURES Abdominal neuroblastomasThe most common presenting symptom is an abdominal or flank mass. Thoracic neuroblastoma - a posterior mediastinal mass on chest radiograph and may cause respiratory distress or cord compression. Neck tumor - presents with a cervical mass. Pelvic tumor - usually involves the organ of Zuckerkandl.

27. NEUROBLASTOMA -DIAGNOSIS. • cate­cholamine metabolites in the urine. Over 80 per cent of patients excrete The most common by­products assayed -VMA and HVA [homovanillic acid] • Plain radiography shows fine, stippled calcification in 50 per cent of cases. • Abdominal ultrasound examination shows the anatomical margins and extent of the disease. • CT -demonstrates calcium in 80 per cent of cases and accurately evaluates intraspinal extension as well as hepatic and renal metastatic disease. • MRI is - supersede CT in many patients. It will also evaluate bone marrow metastases. • Meta-iodobenzyl-guanidine (MIBG, ] is metabolised by neuroblastoma cells -used for imaging--especially in small residual tumours not evident on other conventional imaging studies. • Bone-seeking isotope (technerium-99m)- bone involvement,

28. NEUROBLASTOMA IMMAGING & STAGING CT is the best imaging study for patients with neuroblastoma and should be performed to determine the extent of disease. Useful nuclear medicine studies include a technetium bone scan and a 131I-MIBG scan.

29. NEUROBLASTOMA -TREATMENT Treatment depends on the stage of disease. Stage I and II tumors can be resected. Most abdominal tumors involve major vessels. Unresectable abdominal tumors; Biopsy-radiation or chemotherapy, Then syrgery [if possible] Radiation therapy is useful in : a-nodal disease b-infants with spinal cord compression. chemoresponsive. Well responsive

30. NEUROBLASTOMA -TREATMENT • Surgical excision - mainstay of cure in localised disease, disease confined to one side of the midline delayed treatment following control by chemo- and radiotherapy. • No role of surgery as primary treatment in case of widespread disease at presentation • Multi drug chemotherapy and radiotherapy are instituted in advanced /widespread disease. • cure rare remains low with an • overall survival rare of 30—35 per cent. • Age has an important favourable influence on prognosis — the younger the patient the better the prognosis, and children in the first year of life have a long-term survival rare of 70 per cent.

31. PHEOCHROMOCYTOMA • It owes its name to the presence of chromaffin granules. • usually pinkin colour composed of large, differentiated, sympathetic gan­glion cells and a few fibres, enclosed in a delicate capsule. • soft, vascular tumour usually less than 5 cm in diameter but occasionally very much larger.

32. PHEOCHROMOCYTOMA • The ‘10 per cent tumour’ - 10 per cent are bilateral, malignant, extra-adrenal, multiple, familial and occur in children. • 90 per cent of phaeochromocytoma arise in the adrenal medulla • May be found anywhere along the paraganglionic system. The most common extra-adrenal site is the organ of Zuckerkandl at the aortic bifurcation and less common sires are the urinary bladder, renal hilum, chest and neck. • Extra-adrenal tumours - incidence of malignancy of 25—40 per cent.

33. PHEOCHROMOCYTOMA Clinical features • Both sexes, early adult life or middle age. • Produces intermittently or continu­ously, excess of adrenaline, and especially of nor-adrenaline: the ratio of the latter to the former often being as high as 20:1 causing hypertension which is either paroxysmal or persistent. • The persistent hypertension indicates a late stage of the disease. • 0.5per cent- 3 per cent of cases of hypertension • All patients under 60 years of age who suffer from sustained arterial hypertension deserve routine tests to confirm or exclude a phaeochromocytoma. • Untreated, it progresses to a fatal termination from cardiac dysrhythmia or cerebral haemorrhage. • A component of MEN II.

34. PHEOCHROMOCYTOMAClinical features • Sudden attacks of panic and anxiety-A typical complaint is that of fear — ‘I thought I was going to die’. • The most common symptoms, in order of frequency, are: headache (55 per cent), palpitation, vomiting, swearing, dyspnoea, weakness and pallor — i.e. the symptoms of adrenal overdosage. The paroxysmal attack may vary from a few minutes to some hours. The blood pressure may be very high and hyperglycaemia present.

35. PHEOCHROMOCYTOMAClinical features D/D Symptoms may be mistaken for: Hyperthyroidism, Hypo­calcaemia, An acute anxiety state, Paroxysmal atrial tachycardia Carcinoid syndrome. failure to think about phaeochromocytoma is the main cause of delayed diagnosis

36. PHEOCHROMOCYTOMAAssociated Syndromes Ten percent of pheochromocytomas occur as part of inherited conditions. Bilateral medullary pheochromocytomas components of multiple endocrine neoplasia (MEN) types IIA and IIB. May occur in families without other manifestations of MEN syndromes. They occur in 25 percent of patients with von Hippel–Lindau's disease and in 1 percent of patients with neurofibromatosis and von Recklinghausen's disease.

37. PHEOCHROMOCYTOMADiagnostic tests The basis of the laboratory diagnosis is measurement of elevated catecholamines and metabolites in urine and blood. • Urine studies. Confirmation of the diagnosis made by: measurement of free catecholamines, VMA Metadrenalines (metanephrines) in 24-hour collections Patients with phaeochrornocytoma usually excrete: free catecholamines in excess of 100 ag/24 hours, VMA in excess of 7 mg/24 hours metadrenalines in excess of 1.3 mg/24 hours. Laboratories vary in the reliance they place on these various estimations; False-positive elevations of metadrenaline excretion in patients taking monoamine oxidase-inhihiting drugs in those who have recently had angiographic contrast studies.

38. PHEOCHROMOCYTOMAIMAGING-Localization • Ultrasonography • Computerised tomography method of choice for localisation with an accuracy of 90—95 per cent • Arterio­graphy and selective venous sampling.-obsolete. • Radionuclide imaging. -, iodine-labelled MIBG localisation of adrenal and ectopic phaeochromocytomas. Only abnormal areas of adrenergic tissue show uptake of MIBG- normal adrenals do not visualise. MIBG scanning may be particularly valuable in locating an ectopic phaeochromocytoma when CT shows normal adrenals

39. PHAEOCHROMOCYTOMATreatment Medical and surgical management of pheochromocytoma ---------- Mayo - described in the United States Crout et al 1960s, elucidated the biochemical pathways and diagnostic catecholamine studies, allowing diagnostic ability prior to exploration.2

40. PHAEOCHROMOCYTOMAPreoperative preparation • Catecholamine-secreting Tumours are a challenge • Hypovolaemic because of the contraction of the vascular bed • Handling of the tumour raise catecholamine levels up to 600-fold . • Severe hypotension may follow removal of the tumour. • Preoperative preparation. Effective blockade of the effects of high circulating catecholamines has significantly reduced the operative mortality and is mandatory. • The alpha-adrenergic blocking drug phenoxybenzamine in an initial dose of 20—40 mg/day is increased until hypertension is controlled and mild orthostatic hypotension induced. Preparation takes 1—3 weeks. • Beta-blocking drug propranolol is added for 3~7 days before operation to control tachycardia and arrythmias. • Extra fluids should be given iv.

41. PHAEOCHROMOCYTOMAOperation • During surgery, intravenous infusions of alpha- and beta-blocking drugs are - determined by the blood pressure, pulse rate and central venous pressure. • Hazardous phases during the induction of anesthesia, positioning of the patient on the operating table, when the tumour is manipulated, immediately after removal of the tumour. Sodium nitroprusside, a direct peripheral vasodilator • Multiplicity of tumours (intra- and extra-adrenal) and the need to avoidexcessive tumour manipulation necessitate a generous transabdominal approach. The tumour should be manipulated as little as possible and the main adrenal vein ligated as a first step. Inadvertent rupture of the tumour should be avoided as this may result in local spread and recurrence of even apparently benign tumours.

42. PHAEOCHROMOCYTOMAMALIGNANT PHEOCHROMOCYTOMA Metastases may not develop for years. The basic principle is to resect recurrences of metastases whenever possible and to treat hypertension with appropriate blockade. Radiotherapy. Painful bony metastases Chemotherapy with cyclophosphamide, vincristine, and dacarbazine has been beneficial. Five-year survival is 36–60 percent.

43. ADRENALECTOMY • Open Surgery • Adrenalectomy may be done using a posterior approach through the bed of the twelfth rib • laparoscopy - using a lateral approach. The laparoscopic approach is suited for small aldosteronomas or cortisol-secreting adenomas or hyperplastic adrenal glands. It is not recommended for Phaeochromocytoma because need for tumor manipulation and because the adrenal vein cannot be controlled early.