Michael-John Devlin (CT1)
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*
*Discuss the individual presentation, investigation, treatment and prognosis of the following endocrine cancers:
*Thyroid
*Adrenal
*Neuroblastoma
*Also highlight MEN and other syndromes associated with endocrine cancers
*
*1% of all UK malignancies and 0.5% of all
cancer deaths
*More common in women 2.5:1
*Preponderance in 4th and 5th decades with
median age of presentation 47 years
*Relatives of patients with thyroid cancer have
a x10 increased risk
* Differentiated
* Papillary and Follicular
* Only well established RF is previous H&N irradiation
* Few rare inherited syndromes like FAP and Gardners
* Undifferentiated
* Anaplastic
* Typically older population with 20% having previous differentiated thyroid cancer
* Up to 50% have history of multinodular goitre
* Medullary
* 75% sporadic
* If more than one case in a family think of familial disease eg MEN 2a and 2b or isolated familial medually thyroid cancer.
* Others
* Lymphoma
* Metastases from breast or colon cancer
*
*Medullary carcinoma
*Prophylactic thyroidectomy at early age often
appropriate if known carrier of predisposing
gene (MEN 2)
*Calcitonin problematic
*Molecular analysis for germline RET
**Differentiated
* Incidental microcarcinomas or painless lump
*Clinical regional lymph node involvement in 50% children
*Disseminated disease 2-10%
*Clinically euthyroid
*Undifferentiated
*Rapidly enlarging neck mass which may be painful
*Confluent bilateral lymphadenopathy
*90% regional or distant spread at diagnosis
*Medullary
*Painless neck lump
*50% cervical lymph nodes
*
*FBP, LFT and U&E
*TFT
*Calcitonin
*HR thyroid ultrasonography with fine needle
aspiration
*? CT/MRI neck
*Staging with CT chest/liver and skeletal survey
**Differentiated
*Based on TNM staging and takes into account age of
patient
*Undifferentiated
*Very poor prognosis and all effectively stage IV
*Medullary
*Staging based on tumour size, local invasion, nodal
disease and presence of metastasis. Unlike
differentiated classification age is not a factor.
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*Surgery
*Radio-Iodine
*Radiotherapy
*Chemotherapy
**Differentiated
* Unilateral total lobectomy
* Total thyroidectomy
* More extensive resections
* Complications: hypoparathyroidism, recurrent laryngeal nerve injury and superior laryngeal nerve injury
*Undifferentiated
* Usually inoperable at presentation
*Medullary
* Preoperative screening for phaechromocytoma and hyperparathyroidism
* Total thyroidectomy, central and ipsilateral neck node dissection
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* 131I is used for ablation of residual thyroid tissue, assessment of diseases recurrence and treatment of residual or recurrent disease
*Reduced risk of local recurrence by 60%
*Prolongs disease free survival
* Increases sensitivity and specificity of subsequent screening
*Preparation for 131I includes:
* Total thyroidectomy one month previous
* No thyroid hormone replacement
* Low iodine diet and avoidance of iodine medications
* Confirm biochemically hypothyroid
* Men should be offered sperm storage
*Post ablation diagnostic 131I scans preformed
and serum thyroglobulin should become
undetectable.
*Replacement of thyroid hormone with lifelong
suppression of TSH
*
* Differentiated
* Those tumours that don’t concentrate radio-iodine, if the primary tumour is large (pT4), extracapsular spread or lymph node involvement or other poor prognostic features
* Typically 60 Gy in 30 fractions in two phases with shielding in second phase to avoid exceeding spinal cord tolerance.
* Also Palliative role
* Undifferentiated
* Most commonly palliative intent for local control of inoperable tumours or symptomatic mets
* Medullary
* Post-operatively for macroscopic remnant to maximise local control.
* Can be used pre-operatively to make an inoperable tumour operable.
*
*Very limited role
*Only if other modalities are no longer
appropriate and patient remains fit
*Response rates poor (<30%), incomplete and of
short duration
*Doxorubicin
*
*Differenatied
*Most recurrance within 5 years
*Regular examination, serum T4, TSH and TG on
each visit. Increased TG in presence of supressed
TSH requires investigation
*Medullary
*Clinical examination, serum calcitonin levels and
screening for familial diseases
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*Differentiated
*>90% 10 year survival (98% Papillary, 92% follicular)
*Undifferentiated
*Aggressive cancer with very poor prognosis
*Time from first symptoms to death is 3-7 months
*5-14% 5 year survival
*Medullary
*No effective treatment for advanced disease but may live for years despite high metastatic load (median survival of stage IV disease is 5 years)
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* Adrenocortical
* 1 per 106 population
* Unknown aetiology, rare familial cases
* Bimodal age distribution; peaks before age of 5 and then in 4th-5th decades
* 60% non-functioning, 40% secreting oestrogens, testosterone and/or aldosterone
* Medullary
* 0.6 per 106 population
* 10% familial including MEN2 and occasionally VHL
* Commonest is phaeochromocytoma which exhibits the “Rule of 10”
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*Adrenocortical
* Incidental
*Pressure symtoms
*Virilization, Cushings, feminization and hypertension
*Medullary
* Incidental
*During screening of familial syndromes
*Classical presentation of headache, sweating, tachycardia/palpitations
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* Family history
* FBP, U&E, LFT
* Plasma catecholamines
* Plasma renin and aldosterone activity ratio
* Urinary VMA and catecholamines
* Chromogranin assays
* Serum and urinary cortisols
* Blood oestrogen and testosterone
* CXR
* USS, CT, MRI abdomen to assess for potential metastatic disease
* USS thyroid (MEN)
* Selenocholestrol imagine – cortical tumour
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*Surgery
*Only treatment to achieve cure n benign disease
or patients with localised malignant disease
*Open or laprascopic
*Preoperative need to correct electrolyte
abnormalities and control hypertension
*Non-surgical
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*Adrenocortical tumours
*Mitotane
*Metyraone, Aminoglutethamide and ketoconazole
*Chemotherapy
*Radiotherapy
*Medullary
*Anti-hypertensive
* 131I-MIBG
*Chemotherapy (dacarbazine, vincristine and cyclophosphamide)
*Radiotherapy
**Adrenocortical
*Almost all benign are cured with surgery
*Poor prognosis with malignant disease, untreated survival being 3-9 months improving to 14-36 months with surgery
*Medullary
*Surgery is not always curative even in benign disease
*Long term monitoring required
*5 year survival for malignant phaeochromocytoma is <50% however some patients may live for many years without significant symptoms.
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*Commonest extracranial solid tumour in childhood
*Peak at 1-3 years
*Arise in sympathetic nervous tissue (60% adrenal)
*Pathology ranges from undifferentiated, small, round
cell and highly differentiated ganglioneuroblastoma
*Investigated with abdominal USS, CT/MRI Chest and
abdomen, MRI spine, urinary catecholamines, bloods
including serum LDH and serum neurone-specific
enolase (NSE)
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*Depends on stage and presence of certain
genetic features that may indicate a less good
prognosis (n-myc oncogene)
*Watch and wait
*Surgical clearance
*Neoadjuvant Chemotherapy
*Radiotherapy
*
*Depends on stage, genetics and age of
diagnosis.
*Children <1 year have good prognosis even in
presence of widely disseminated disease (85%
overall survival for stage 4S)
*Children >5 have an overall survival of <40%
with neuroblastoma of any age
**Syndromes with multiple benign or malignant endocrine
neoplasms
*MEN-1
* Menin gene on C11
* Parathyroid, Pituitary and Pancreas
*MEN-2a
* Ret gene on C10
* Parathyroid, Phaeochromocytoma, Medullary Thyroid
*MEN-2b
* Ret gene on C10
* Parathyroid, Phaeochromocytoma, Medullary Thyroid, Marfanoidand mucosal neuromas
*Carney Complex
*Gardners Syndrome
*Beckwith-Wiedemann Syndrome
*Li–Fraumeni syndrome
*Cowen Syndrome
*Tuberous sclerosis
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