adrenal glands 4 tumors

Pheochromocytoma

  • rare tumors that produce, store, and secrete catecholamines.
  • Clinical syndrome caused by hypersecretion of catecholamines
  • Can occur in any sympathetic ganglion in the body
  • More than 90% from adrenal medulla (10% extra-adrenal)
  • Arise from the chromaf n cells of the adrenal medulla or from the sympathetic ganglia if extra-adrenal.
  • „A rule of 10”: 10% extradrenal, bilateral, malignant, part of MEN IIA or IIB, familial syndromes (vHL, NF), 10x more often in children

manifestation

  • due to catecholamine excess often intermittent
    -Hypertension – paroxysmal or constant
    -Triad: headache, palpitations, sweating
    -Pallor > flushing
    -Anxiety, panic, tremor
    -Abdominal and chest pain
    -Constipation or diarrhoea
    -Orthostatic hypotension

Clinical features

Precipitation of symptoms by:
• emotional stress,
• exercise
• abdominal pressure
• anesthesia
• tyramine-containing foods

Diagnosis

  • Plasma metanhephrine and normetanephrine
    -metanephrine > 0,61 nmol/l
    -normetanephrine >0,31 nmol/l
  • Methanephrines in 24-hour urine collection (2-3x)
  • Plasma chromogranin A
  • Clonidine suppression test
    -0,3mg/kg orally, plasma catecholamines measured before and after 3 hours
  • Urine/serum epinephrine and norepinephrine levels—if the epinephrine level is elevated, the tumor must be adrenal or near the adrenal gland (organ of Zuckerkandl) because nonadrenal tumors cannot methylate norepinephrine to epinephrine

Imaging

• CT scans of the abdomen - tumor is often large
• MRI with „chemical shift”
• Extra-adrenal tumors
-Scanning with 131I-MIBG – specific uptake in sites of sympathetic activity
-Octreoitide scan
• PET (positron emission tomography)

Treatment

  • Surgical - if this is possible
  • Medical preoperative and perioperative treatment
    -α-blockade: phenoxybenzamine, prazosine (up to 2 weeks before)
    -Prior or during surgery: β-blockade
    -In case of sudden severe hypertension: sodium nitroprusside infusion
    -Plasma volume repletion (blood transfusion, colloids)
  • Chemotherapy or radionuclide treatment with 131I-MIBG in malignant pheochromocytoma

Incidental adrenal mass („incidentaloma”)

  • Unsuspected and discovered in 1% of abdominal scans performed for other purpose
  • Should be evaluated for evidence of hormone secretion and malignancy
  • Tests to reveal secretory activity:
    24h UFC, 1mg dexamethasone suppression test, DHEAS, serum testosterone, urine metanephrins, PA/PRA ratio
  • Exclusion of malignancy
  • Removal of large (> 4cm) and all hormone-
    secreting tumors
  • Small, inactive masses should be reassessed in 3-6 month, then anually and removed if growth occurs or if hormone secretion developes

Laboratory ndings: hyperglycemia, hyperlipidemia, hypokalemia

  • rule of 10s for Pheochro- mocytoma tumors
    • 10%arefamilial
    • 10% are bilateral (suspect MEN type II)
    • 10%aremalignant
    • 10%aremultiple
    • 10%occurinchildren
    • 10%areextra-adrenal (more often malignant)— The most common site is the organ of Zuckerkandl, which is located at the aortic bifurcation.

ADRENAL MALIGANCIES

adrenocortical carcinoma

  • 50-70% of adrenocortical carcinomas secrete steroid hormones
  • Functioning secrete: cortisol, androgens or aldosterone alone or in combination
  • Nonfunctioning - present clinically as abdominal or flank pain, a palpable tumor or as an adrenal mass discovered by an imaging procedure
  • most suggestive clues of malignancy:
    -rapidly progressive CS or/and virilisation in woman
    -tumor size greater than 6 cm and evidence of locally invasive or metastastic disease (liver, lungs)
    -↑↑ urinary 17 KS, ↑↑ DHEA
    -malignancy is frequently not suspected until the tumor is examined histological
    (non-secreting, „ silent” tumors)
  • TREATMENT:
    Surgery is the treatment of choice
    Mitotane is the drug of choice
    -produces partial or complete tumor regression
    -reduces production of adrenal hormones
    -improves survival
    -should be started immediately after surgery
    Other chemotherapeutic agents and radiation therapy are not effective
  • PROGNOSIS:
    The mean survival is about 15 months
    The 5-year survival rate is approximately 20%

Malignant pheochromocytoma

  • 10-15% of pheochromocytomas
  • Similar clinically at presentation to the benign form
  • Malignancy is highly suggestive by:
    -tumor size > 6 cm
    -evidence of extradrenal spread (lymph nodes, liver, lungs, bones)
    -↑↑ urinary excretion of dopamine
  • TREATMENT:
    Surgery is the treatment of choice
    Alpha-aderenergic blocking agents and alpha- methyltyrosine (catecholamine synthesis inhibitor)
    long-term therapy for patients with unresectable tumor
    Chemotherapy, palliative irradiation
    131I –MIBG therapy
  • PROGNOSIS:
    he 5 –year survival rate is 40-50%

Metastases to adrenal glands

  • The vascular adrenals are frequent site of bilateral metastatic spread from cancer of the lung, breast, stomach, pancreas, colon, kidney and from melanomas and lymphomas
  • Up to 33% of patients may have subtle adrenal insufficiency

Therapeutic steroid therapy

  • Replacement for endocrine deficiency states („physiologic doses” - namely 7,5 mg of prednisolone or 30-40 mg of hydrocortisone)
  • Non-replacement (non-endocrine conditions):
    short-term use – only small risk of side –effects
    long-term application („supraphysiologic” anti- inflammatory or suppressive doses) danger depends on a dose and on a time of therapy
  • Rules of long-term non-replacement:
    need for high-dose steroids should be critically assessed
    (minimal necessary dose, consideration of steroid- sparing agents)
    Prophylactic therapy for osteoporosis should be introduced
    Therapy must never be stopped suddenly
    Most of dose must be given in the morning
    Double doses should be taken during fever, accident and other stress
  • Adverse effects of non-replacement:
    Physiological: adrenal/pituitary depression
    Pathological: iatrogenic CS with subsequent metabolic, cardiovascular, gastrointestinal, dermatologic, psychiatric, orthopedic complications and increased susceptibility to infection (also fungal and TB)
  • Steroid cover for operative procedures:
    For any patient receiving steroids within the last 12 months
    Simple procedures (endoscopy, dental extration) – HC 100 mg i.m. in a premedication
    Surgery / delivery:
    -premedication with 100 mg of HC
    -HC 50-100 mg i.v. every 6 hours for 3 days, than higher oral doses for next 2-3 days

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