This document discusses endocrine cancers including thyroid, adrenal, neuroblastoma, and syndromes associated with endocrine cancers. Thyroid cancers are more common in women and relatives have a 10x increased risk. Differentiated thyroid cancers include papillary and follicular, while undifferentiated include anaplastic and medullary. Adrenal cancers are rare and secreting hormones in 40% of cases. Neuroblastoma is the most common extracranial solid tumor in childhood. Multiple endocrine neoplasia (MEN) syndromes like MEN1 and MEN2a/2b are also discussed.

1. *
Michael-John Devlin (CT1)

2. *
* 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

3. *
* 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

4. * 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

5. *
* Medullary carcinoma
* Prophylactic thyroidectomy at early age often
appropriate if known carrier of predisposing
gene (MEN 2)
* Calcitonin problematic
* Molecular analysis for germline RET

6. *
* 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

7. *
* 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

8. *
* 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.

9. *
* Surgery
* Radio-Iodine
* Radiotherapy
* Chemotherapy

10. *
* 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

11. *
* 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

12. * Post ablation diagnostic 131I scans preformed
and serum thyroglobulin should become
undetectable.
* Replacement of thyroid hormone with lifelong
suppression of TSH

13. *
*
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.

14. *
* 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

15. *
* 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

16. *
* 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)

20. *
* 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”

21. *
* Adrenocortical
* Incidental
* Pressure symtoms
* Virilization, Cushings, feminization and
hypertension
* Medullary
* Incidental
* During screening of familial syndromes
* Classical presentation of headache, sweating,
tachycardia/palpitations

22. *
* 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

23. *
* 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

24. *
* Adrenocortical tumours
* Mitotane
* Metyraone, Aminoglutethamide and ketoconazole
* Chemotherapy
* Radiotherapy
* Medullary
* Anti-hypertensive
* 131I-MIBG
* Chemotherapy (dacarbazine, vincristine and
cyclophosphamide)
* Radiotherapy

25. *
* 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.

28. *
* 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)

29. *
* 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

30. *
* 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

32. *
* 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, Marfanoid
and mucosal neuromas

33. *
* Carney Complex
* Gardners Syndrome
* Beckwith-Wiedemann Syndrome
* Li–Fraumeni syndrome
* Cowen Syndrome
* Tuberous sclerosis