multiple endocrine neoplasia Flashcards
definition of MEN
epidemiology of MEN
MEN1 - estimated prev worldwide - between 1 in 50000 and 1 in 500000. Prolactinomas most common tumours
MEN2 - in 1000 families worldwide in 2001, most cases MEN2A. Medullary thyroid cancer most common presenting symptom, in nearly all genetic carriers by adulthood unless prophylaxis
signs and symptoms of MEN1
young age
+ve FH
clinical features of kidney stones - excess PTH from parathyroid hyperplasia = hypercalcirian can cause nephrolithiasis
facial angiofibromas or collagenomas
irregular menses - prolactin or cortisol elevation from prolactinomas or pit adenomas = secretion of cortisol. Mass in pit can = hypopit
visual changes - pit masses
infertility - hypersecretion of prolactinomas or suppression of gonadotrophins due to large functioning or non-functioning pit adenomas
clinical features of acromegaly
clinical features of thyrotoxicosis
signs and symptoms of MEN2
young age
+ve FH
episodic triad of sweating, palpitations, headache - phaeochromocytomas with episodic hypersecretion of catecholamines
clinical features of kidney stones
mucosal neuromas (2B) on lips tongues and eyelids
arm span and upper-to-lower-body-segment ratio (2B) - marfanoid body habitus
palpable thyroid nodule
RF for MEN
FH
RET proto-onchogene mutation
MEN1 mutation
investigations for MEN
MEN2 - serum calcitonin - high = medullary thyroid cancer
MEN2 - serum carcinoembryonic ag - high - medullary thyroid ca (not specific)
MEN2 - plasma metanephrines - high - phaeo
MEN2 - 24hr urine metanephrines and catecholamines - high - 2x upper limit normal suggest phaeo
MEN2 - thyroid biopsy - atypical cells or medullary thyroid ca
serum PTH and Ca - high - primary hyperPTH
24hr urine Ca high suggets hyperPTH, low to normal indicate vit D deficiency
MEN1 - fasting serum gastrin - high - gastrinoma (not specific)
MEN1 - serum chromogranin A - high - neuroendocrine tumours
MEN1 - serum prolactin - high - prolactinoma, macroadenoma (due to pit stalk compression), GH secreting adenomas
MEN1 - IGF-1 - high - hormone secreting adenomas
aetiology of MEN
autosomal dominant mutations that can be inherited or occur sporadically
MEN1 gene mutations responsible for 80-90% of MEN1 - genotype to phenotype correlations are weak
RET protoonchogenes are responsible for almost all MEN2 - phenotypes of MEN2a 2b and familial medullary thyroid ca predicted by mutations
mechanism of MEN1
MEN1 genes make nuclear proteins called menin
menin forms complexes and modulates activity of transcription factors
MEN1 tumours result from somatic mutations, which disrupt the normal MEN1 alleles in susceptible cells
all MEN1 tumours exhibit loss of normal MEN1 alleles along germ line mutations - implying menin has tumour suppresive roles
mutation types (missense or nonsense) may be relevant to phenotypes
summarise RET
protoonchogenes
encode large transmembrane proteins that transduce growth and differentiation signals in developing tissues, including those derived from neural crests
what is dx of MEN 1 based on
2 MEN1 tumours or more
or 1 tumour and a 1st degree relative with the condition
or on genetics alojne with a diagnosed pathogenic mutation of MEN1
MEN1 associated tumours
endo
- parathyroid adenomas
- pit addenomas
- gastrinomas and other enteropancreatic tumours
- neuroendocrine/carcinoid tumours from bronchial/gastric/thymic origin
- adrenal cortical tumours
- CNS tumours inc meningiomas
- thyroid tumours
non-endo
- cutaneous tumours
- lipomas
- facial angiofibromas
primary hyperthyroidism is commonly associated
tumours associated with MEN2a
medullary thyroid ca
phaeo
multigland parathyroid adenomas with hyperparathyroidism
Hirschsprung’s disease as an associated feature
cutaneous lichen amyloidosis as an associated feature
patients with MEN2B may have…
medullary thyroid ca
phaeo
marfanoid body habitus
mucosal intestinal ganglioneuromatosis
