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

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*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

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*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

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*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

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* 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.

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*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

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*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

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*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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