men 1

1. Multiple endocrine neoplassia

2. MEN I
• Components:-
(1) Classical lesions:- Endocrine tumors of
parathyroid gland, endocrine pancreas-
duodenum complex, and anterior pituitary gland
(2) Other lesions:- foregut carcinoids (in the
thymus, bronchial tree, and the stomach),
adrenocortical hyperplasia; and non endocrine
tumors, such as meningioma, ependymoma,
eiomyoma, lipoma, facial angiofibroma, and
collagenoma

4. Epidemiology
• Incidence
Overall (postmortem studies) 0.25%
Primary hyperparathyroidism 1–18%
Gastrinomas 16 – 38 %
Pituitary tumors <3 %
• M:F = 1
• Age 5 to 81 yr

5. Etiopathogenesis
• Familial:- Autosomal dominant with a high
degree of penetrance
• Sporadic :- 8 to 14% of patients with MEN 1
• Mutations of the MEN-1 tumor suppressor
gene on chromosome 11q13 encoding for
‘MENIN’ protein
• Resulting in DNA replication and repair.

6. Diagnosis

7. Genetic diagnosis
• Complete MEN-1 gene sequencing - best
method and positive in 70% to 90% of typical
MEN-1 cases.
• Multiplex ligation-dependent probe
amplification (MLPA) assay –recent and for
detection of large deletions occurring in 4% of
MEN-1 cases
• Negative genetic testing cannot exclude the
syndrome

8. • Candidate - index patients and first-degree
relatives
• Offer at the earliest opportunity
• Genetic counseling before testing

9. Surveillance and screening
• Recommended in presymptomatic gene
carriers
• Started in first decade of life
• By a combination of biochemical tests and
imaging studies

11. Primary HPT (pHPT)
• Primary HPT - Commonest (90%) and first
detected endocrinopathy
• Often diagnosed around 20 years of age, and
>95% before age of 40 years

12. Clinical features
• Decrease in bone mineral density,
nephrolithiasis, fatigue, weakness, asthenia,
depression, and typical concentration
difficulty

13. Diagnosis
• Biochemical:- raised ionized or total-albumin
corrected serum calcium and raised serum
parathyroid hormone (PTH)
• Localisation:- Recommended in recurrent
settings

14. MEN 1 v/s other causes of pHPT
• Mild hypercalcemia, severe is rare,
• Earlier age at onset (20 to 25 yr vs. 55 yr),
• Greater reduction in bone mineral density
• Male/female ratio (1:1 vs. 1:3)

15. Pathology
• Asymmetric nodular hyperplasia resulting in
multiple tumors.
• Most benign
• Carcinoma rare (only 3 case reports)

16. Surgical management
• Challenge:- high recurrence rate
• Issues:-
Open bilateral neck exploration v/s minimally
invasive parathyroidectomy
Subtotal parathyroidectomy v/s total
parathyroidectomy

17. Subtotal parathyroidectomy
• Surgery of choice as primary surgery
• 3 to 3.5 gland removed
• Remnant - smallest, most normal gland,
vascularity verification
• Chance of persistent or recurrent
hypercalcemia - 40 to 60% within 10 to 12 yrs
• Chance of hypocalcemia (requiring long-term
calcitriol) - 10 to 30%

19. Total parathyroidectomy
• Auto transplantation (forearm or
subcutaneous fat on the thorax or abdomen)
• 10 fresh parathyroid pieces each 1 mm in size
• High risk of hypoparathyroidism
• Chance of recurrent hypercalcemia >50%
• Required in presence of extensive disease or
in recurrence
• For grafting - smallest, least diseased gland

20. Supernumary parathyroid tissue
• Cervical thymectomy + clearance of
perithyroid fat
• Contribute for 15 % of recurrence

21. • Intraoperative PTH determination:- Requires
special criteria to avoid false results, implying
evaluation 20 minutes after glandular removal
and that an end point value within the assay
limits is reached

22. • Cryopreservation of parathyroid tissue:-
recommended if facilities are available - risk
for remnant ischemia and permanent
hypoparathyroidism.

23. parathyroid tissue verification in
resected specimens
• Needle biopsy aspiration with rapid PTH
determination has replaced frozen sections

24. Re -Surgery
• Localization studies –
1. USG,
2. Sestamibi scintigraphy,
3. CECT,
4. PET with methionine tracer,
5. USG guided FNA with PTH measurement,
6. Selective venous sampling with rapid PTH
determination
• Concordant results of two investigations are
required

25. Endocrine Pancreatic and Duodenal
Tumors
• Incidence - 30 to 80% in different series
• Nonfunctioning (PPoma) 20 to 55 %
• Gastrinoma – commonest (40%)
• Multiple & Earlier age of onset

26. Risk of Metastatic
• Presence of a clinical syndrome of hormone
excess (up to 50% risk)
• Size > 3 cm
• 25–40% of patients with pNET >4 cm develop
hepatic metastases, and 50–70% of patients
with tumors 2–3 cm in size have lymph node
metastases

27. Gastrinoma
• Age of onset after 30 years
• Microadenoma, Multiple & deep mucosal
• Gastrinoma triangle
• Pancreatic Gastrinoma –
large & early liver metastases
concomitant nonfunctioning NET

28. • Clinical Features - ZES
• Biochemical Diagnosis:- Increased fasting
serum gastrin concentration in association
with increased basal acid output (gastric pH
<2) and if needed iv provocative tests with
either Secretin (2 U/kg) or calcium infusion (4
mg Ca/kg/h for 3 h)

29. Localization
• Ultrasonography, Endoscopic USG, CT, MRI,
Selective abdominal angiography or
Somatostatin-receptor scintigraphy
• The combined use of intraarterial calcium
injections with hepatic venous gastrin
sampling

30. Failure of localization
• In MEN1, ZES does not develop in the absence
of primary hyperparathyroidism, and
hypergastrinemia has also been reported to
be associated with hypercalcemia

31. Treatment
• Surgical:-
(1) Controversial role
(2) Indication - size > 2 cm, symptomatic
(3) C/I - Liver metastases
(4) Duodenectomy or Limited resection
(5) Whipples most effective but less
preferred (cure rate > 65%)

32. Limited resection v/s Whipples
• Best cure rate with Whipples – 65%
• Excellent survival with limited resection – 52%
and 100% at 15 yr in patients with and
without metastases, respectively

33. Non surgical treatment
PPI – Backbone
UGIE Surveillance – ulcer, carcinoid

34. Treatment of metastatic Gastrinoma
• Chemo - Streptozotocin and 5-FU
• Somatostatin analogs - octreotide or
lanreotide
• Hepatic artery embolization
• Administration of human leukocyte interferon
• Removal of all resectable tumor

35. Insulinoma
• Incidence 10 to 30% of pNET
• Affected age group – younger than 40 yr
• Usually single & >5 mm in diameter but
concomitant other pNET may exist
• Hypoglycemic symptoms
• 72 hours fasting test – diagnostic

36. • Preoperative localization – EUS, MRI, CT or celiac
axis angiography, selective intraarterial
stimulation with hepatic venous sampling, and
intraoperative direct pancreatic USG
• Surgery - Enucleation – commonly performed,
• Other options:- Distal pancreatectomy or partial
pancreatectomy, or excision of all the
macroscopic pancreatic tumors with enucleation
of nodules in the remaining pancreas

37. • Monitoring the insulin/glucose ratio during
surgery
• Metastatic disease - Streptozotocin, 5-FU and
Doxorubicin or hepatic artery embolization

38. Nonfunctioning pNET
• Commonest pNET
• Malignant pNET - commonest cause of death
in MEN1
• Worse prognosis than functioning tumors
• Indication of surgery – size >1 cm &
symptomatic

39. Target therapy
• Sunitinib & Everolimus are of proven benefit
(increase survival) in advanced pNET but these
studies don’t specify MEN 1 status, so
probably advanced MEN 1 patients may get
benefitted from these drugs.

43. Pituitary tumors
• Incidence - 15 to 50%
• Age of onset - 5 yr of age to as late as the
ninth decade, and the mean - 38.0+/-15.3 yr
• F > M
• Macroadenoma – 85%
• 1/3 – invasive histology – locally aggressive
but not carcinoma

44. • 60% secrete prolactin, 25% secrete GH, 5%
secrete ACTH and remainder nonfunctioning
• Treatment :- medical therapy (bromocriptine
or cabergoline for prolactinoma; or octreotide
or lanreotide for somatotrophinoma) or
selective transsphenoidal adenomectomy
with radiotherapy reserved for residual or
unresectable

45. Carcinoid tumors
• Overall incidence <3 %
• Bronchial, Thymic and Gastric
• Thymic – aggressive course – increased risk of
death – median time to death 9.5 years
• Most – no Carcinoid syndrome
• No hormonal or biochemical abnormality –
chromogranin ‘A’ absent
• Imaging - CT, MRI, SRS – not a routine
• Treatment - surgery

46. Adrenocortical tumors
• Incidence of asymptomatic tumors - 20–73%
• <10% have hormonal hypersecretion
• Risk of carcinoma - >4 cm in size, atypical or
suspicious radiological features in 1–4 cm
sized, show significant measurable growth
over a 6-month interval and with
hyperandrogenemia
• Treatment – surgical