Multiple Endocrine Neoplasia Flashcards
Multiple Endocrine Neoplasia
Multiple endocrine neoplasia
The table below summarises the three main types of multiple endocrine neoplasia (MEN). MEN is inherited as an autosomal dominant disorder.
MEN type I
3 P’s
Parathyroid (95%): hyperparathyroidism due to parathyroid hyperplasia
Pituitary (70%)
Pancreas (50%): e.g. insulinoma, gastrinoma (leading to recurrent peptic ulceration)
Also: adrenal and thyroid
Most common presentation = hypercalcaemia
MEN type IIa Medullary thyroid cancer (70%) 2 P's Parathyroid (60%) Pheochromocytoma RET oncogene
MEN type IIb 1 P Phaeochromocytoma Marfanoid body habitus Neuromas MEN1 gene RET oncogene
Type 1 MEN - Example Question
A 25 year old woman presents to the endocrinology clinic. She is concerned because her father had a ‘brain tumour’ removed 2 years ago and has now been told he has another tumour in his abdomen after going to his doctor with reflux and indigestion. He has been told it might be a genetic problem and is awaiting testing. She is concerned she might also have the condition and so her GP has referred her to the clinic.
She is currently asymptomatic.
On examination there is no abnormality on the cardiovascular, respiratory, abdominal or neurological examinations.
The doctor explain that the most appropriate person to see would be the geneticist to whom her father has been referred. He asks her to obtain the details if her father is willing to provide them and says that he will refer her. In the meaning time he offers to carry out some screening blood tests.
Given the likely underlying diagnosis, which of the following is most likely to be abnormal?
Cortisol Fasting glucose > Parathyroid hormone Prolactin Thyroid stimulating hormone
This lady’s father is likely to have multiple endocrine neoplasia type 1 (MEN1) as evidenced by 2 MEN1 associated tumours, a pituitary adenoma and a gastrinoma.
Although this lady is asymptomatic, it is important she is offered genetic screening, as the condition is autosomal dominant.
Fasting glucose, parathyroid hormone and prolactin are all biochemical screening tests used for MEN1 associated tumours (insulinoma, parathyroid adenoma and pituitary adenoma respectively). However, hyperparathyroidism is by far the most common initial manifestation and will eventually develop in 90% of MEN1 patients.
ReferencThakker et al. Clinical guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012:97(9)2990-3011)
MEN - Diagnosis and Genetics - Example Question
A 38 year old lady presents to clinic with her 69 year old mother for a follow up appointment. The mother had presented 3 months previously under the acute medical take with headaches, sweating, abdominal pain and wild fluctuations in blood pressure. She is currently being followed up by the appropriate surgical team and her symptoms are currently well controlled with medical treatments. On examination today, you note a lump in her anterior neck and you are given the following blood tests:
Calcium (corrected) 3.68 mmol/l
Phosphate 0.38 mmol/l
Vitamin D3 115 nmol/l (75-200 nmol/l)
Parathyroid hormone 19 pmol/l (0.8 - 8.5 pmol/l)
You have referred the patient to endocrine surgeons for neck biopsies and urgent review. The daughter is concerned she may have the same symptoms later in life. What should you offer the daughter?
Reassurance > Genetic testing for patient and daughter Offer annual follow up for surveillance CT abdomen/pelvis with contrast Serum bone and calcium homeostasis profile
The patient describes features consistent with phaeochromocytoma, the appropriate surgical team would be endocrine surgery, who would arrange for a resection. The new blood tests are suggestive of primary hyperparathyroidism, the neck lumps possible medullary thyroid tumour, resulting in a unifying diagnosis of MEN 2a. The daughter can undergo genetic testing for RET-mutation.
Differentiating between MEN 2A and 2B
Similarities:
- Thyroid carcinomas
- Adrenal tumours
- Parathyroid hyperplasia
However!
MEN 2B typically have a Marfinoid appearance and mucosal neuromas, as well as absence of hyperparathyroidism
(MEN T1 = Pancreatic neuroendocrine tumours, pituitary adenoma, parathyroid hyperplasia)
Suspected MEN Type 1 - Indicator?
High Calcium - useful indicator because high incidence of hyperparathyroid tumours and hypercalcaemia in MEN T1
Pheochromocytoma + Hyperparathyroidism - Example Question
A 57 year old female presents after noticing a lump in her neck. She reports it being non-tender and she is only concerned about it for cosmetic purposes. She reports no other symptoms. Her past medical history includes hypertension and constipation. Her current medications include ramipril, irbesartan, amlodipine and furosemide. No family history is unavailable. On examination, her neck lump is hard, non-tender and measures 2cm by 1 cm, moves with swallowing but not with tongue protrusion. Her heart rate is 84 beats/min and blood pressure 213/130 mmHg. Examination of her joints was unremarkable with no excessive laxity.
Her blood tests are as follows:
Hb 11.2 g/dl Platelets 349 * 109/l WBC 7.2 * 109/l Na+ 138mmol/l K+ 4.2 mmol/l Urea 6.9 mmol/l Creatinine 72 µmol/l Adjusted calcium 3.1 mmol/l Phosphate 0.40 mmol/l
She undergoes an outpatient ultrasound and fine needle aspiration of her neck lump. After her procedure, the recovery nurses were concerned regarding her persistent hypertension and the patient is admitted for further investigation. She develops a mild headache with no visual disturbances, resolving on its own after her blood pressure falls to 182/101 mmHg two hours later. Urinary metanephrine collection was positive.
Which investigation is likely to produce the underlying diagnosis?
> Genetic testing for RET mutation
Genetic testing for germline VHL mutation
Genetic testing for NF2 mutation on chromosome 22
CT chest/abdomen/pelvis with contrast
Urinary calcium collection
The clinical collection of phaeochromocytoma and hyperparathyroidism, should raise suspicion of multiple endocrine neoplasia type 2a, which is a genetic syndrome of near 100% penetrance caused by a mutation of the RET oncogene. The addition of a thyroid lump makes this scenario more suggestive of MEN 2, with medullary thyroid carcinoma completing the diagnosis. MEN2b is subtly differentiated from MEN2a by the lack of hyperparathyroidism and Marfanoid features. Unlikely MEN 1, genetic screening of family members for hyperparathyroidism and germline mutation is useful for long term surveillance and monitoring. VHL and NF 2 mutations refer to von-Hippel Lindau syndrome and neurofibromatosis type 2 respectively: VHL presents classically as a combination of retinal haemangioblastomas, renal cell carcinomas and phaeochromocytomas while NF2 typically present with intracranial tumours, bilateral Schwannomas almost in all patients.
MEN Diagnosis - Thyroid Ca Example Question
A 47 year old man attended his GP after checking his blood pressure at the local pharmacy. When he had it checked it was 179/102 mmHg. The GP confirmed it was high in the surgery at 186/103 mmHg. He started him on ramipril 2.5mg and titrated up the dose to 10mg over the next few weeks. His repeat measurements showed consistently high readings so the GP added amlodipine, which had very little effect despite being tolerated at the maximum dose. After failing to get adequate response with addition of a third agent the GP referred the patient to the endocrine clinic.
Observations showed a blood pressure of 190/105 mmHg and a heart rate of 98 beats per minute. On examination the man was thin with a BMI of 23 kg/m². His apex was diffuse and displaced with normal heart sounds. Chest was clear and abdomen was soft and non tender with no evidence of masses or renal bruits. He was noted to have a hard, painless nodule over the thyroid gland.
24 hour urinary catecholamines were raised and further investigations confirmed phaeochromocytoma. He was treated medically with an alpha blocker then beta blocker whilst awaiting surgery. In this period he had further investigation into the thyroid nodule, which was a cold nodule on radionucleotide scanning.
Which type of thyroid cancer would you expect this to be histologically? > MEDULLARY Papillary Follicular Anaplastic Lymphoma Medullary
This question tests your knowledge of multiple endocrine neoplasias (MEN). This patient could have MEN Type IIa or IIb, which both include phaeochromocytoma and medullary thyroid cancer.
Of all thyroid cancers medullary thyroid cancer accounts for approximately 5% (and of these, 80% will be sporadic rather than associated with MEN).
