disorders of multiple endocrine system Flashcards
1
Q
what are men syndromes
A
autosomal dominant traits that cause predisposition to the development of tumors in two or more endocrine glands
can be malignant or benign
2
Q
where is the most common mutation in multiple endocrine neoplasia type 1
A
90% of patients have a detectable germline mutation in menin
this mutation PREVENTS tumor suppression
3
Q
what is menin
A
tumor suppressor protein encoded by MEN1
4
Q
what age is clinical biochemial manifestations developed by?
A
40
5
Q
what are the most common organs affected by multiple endocrine neoplasia type 1
A
parathyroid
pancreas
anterior pituitary
6
Q
what is the imaging of choice of patients with multiple endcrine neoplasia
A
CT/MRI should be utilized for all suspects organs affected
7
Q
what would you look for on a CT/MRI of a multiple endcrine neoplasia patient
A
location, size, staging and surgical evaluation of tumor
8
Q
what is the most common tumor type in MEN1
A
parathyroid
9
Q
What does a MEN1 parathyroid tumor cause
A
primary hyperparathyroidism (>90% of patients)
10
Q
what is the epidemiology of parathyroid MEN tumors
A
earlier onset than PHPT not related to MEN1
(onset 20-25)
11
Q
what would be the clinical findings of someone with a MEN1 parathyroid tumor
A
asymptomatic mild hypercalcemia with elevated PTH
remember hypercalcemia symptoms are stones, bones groans and moans
12
Q
how do you confirm the location of a MEN1 parathyroid tumor
A
nuclear scan
thats just what the slides say, dont come at me.
13
Q
how do you manage MEN 1 parathyroid tumor
A
surgical removal
rsk of partial (3.5 glands) = risk of surgical failure
risk of total (all 4 glads w autotransplantation) = permanent hypoparathyroidism
14
Q
what is the nonsurgical treatment for MEN1 parathyroid tumors
A
treating hypercalcemia with:
oral cinacalcet (sensipar)
avoid oral calcium and thiazide diuretics
15
Q
what is a GEP-NET
A
gastro-Entero-panreatic neuroendocrine tumors
16
Q
what are the 5 types of GEP-NETs
A
- Gastrinoma - MC
- Insulinoma - 2nd MC
- Glucagonoma
- Vasoactive Intestinal Peptide (Vip) Tumors (VIPomas)
- Pancreatic Polypeptide-Secreting Tumors (Ppomas) and Non-functioning Pancreatic NETs
GIG VP
17
Q
what is a gastrinoma
A
gastrin secreting pancreatic tumor - MC MEN pancreatic tumor
18
Q
what does gastrin do
A
stimulates secretion of gastric acid and assists in gastric motility
19
Q
where are most gastrinomas found
A
duodenum
20
Q
what is the description of a gastrinoma
A
“small, multiple and ectopic”
21
Q
what are zollinger-ellison syndrome
A
gastrinomas of hypersecretion of gastric acid and recurrent peptic ulcers
22
Q
how many patients with MEN1 develope gastrinomas
A
40%
23
Q
what is the clinical presentation of gastrinomas
A
symptoms associated with hyperacidity of stomach:
* gastritis
* PUD
* GERD
* diarrhea
24
Q
skipped slide 14
A
25
what are lab evals of gastrinomas
fasting gastrin: >150 suggestive, >1000 is diagnostic
secretin stimulation test:
+ results - serum gastrin levels post admin >120
26
what must be done prior to lab tests for gastrinomas
must d/c PPI 6 days prior and H2 1 day prior or else could lead to false results
27
how do you manage a gastrinoma
long term high dose proton pump inhibitor w/wo histamine 2 receptor antagonist
PPI: omeprazole, esomeprazole
H2: cimetidine, famotidine
surgery is controversial and outcomes are not definitive
28
what are insulinomas
β-islet cell, insulin-secreting tumors of the pancreas
29
when do insulinomas present
Most often presents between 2nd and 4th decade
30
what is the clinical presentation of insulinomas
hypoglycemia symptoms
* worsen w fasting or exertion
* improves w glucose/carb intake
31
how does hypoglycemia present
here ya go keinan<3
32
what are the most reliable labs for insulinomas, what do they require?
what are the additional labs?
* 72 hour fast
* requires hospital admission for direct supervision
* hypoglycemic symptoms and BG <55mg/dL
additional labs:
plasma insulin (elevated)
c peptide (elevated)
33
how do you manage insulinomas
surgical removal is recommended.
34
how do you treat an insulinoma while wating for surgery or if surgery isnt an option
* frequent carb intake
* oral diazoxide
* IM/SQ ocreotide (sandostatin) when diazoxide can’t be used
35
what is diazoxide (proglycem)
potassium channel activator (inhibits secretion of insulin)
36
what is octreotide (sandostatin)
somatostain analog
high dose inhibits insulin
37
what are glucagonomas
pancreatic tumor that secretes glucagon
38
what is the clinical presentation of glucagonomas
weight loss (MC symptom)
hyperglycemia
necrolytic migratory erythema (that’s the poonani ookalani rash)
stomatitis
39
what is the laboratory evaluations for glucagonomas
elevated BG
elevated fasting blood glucagon level >150
40
how do you manage glucagonomas
control blood sugar (same as DM management)
ocreotide - inhibits glucagon at high doses (also inhibits insulin)
41
when is surgical excision recommended for glucagonomas
if a single lesion is localized at the time of diagnosis
42
what is a VIPoma
a VERY RARE (1 in 10 million)
pancreatic tumor that secretes vasoactive intestinal polypeptide
43
what is VIP functions
* binds to receptors in the intestine leading to fluid and electrolyte secretion into the intestinal lumen
* vasodilation
* inhibition of gastric acid secretion
* bone resorption
* enhanced glycogenolysis
44
what are the clinical findings of VIPomas
* severe diarrhea that is tea colored and odorless >700ml/d
* hypokalemia
* hypomagnesemia
* flushing
* iron and B12 deficiency
* hypercalcemia
* osteoporosis
* hyperglycemia
45
what is the lab eval for VIPoma
serum VIP concentration >75 confirmed by repeat testing
(normal is 0-59)
46
what is the management for VIPoma
* correct fluid, electrolyte and vitamin imbalances
* ocreotide (inhibits VIP and helps diarrhea)
* surgical excision of primary tumor
47
when do you NOT do surgical excision of primary tumor of VIPomas
if there are mets present at diagnosis
48
what are Ppomas and non-functioning pancreatic NETs
non functioning tumors that secrete various substances but do not present clinically with a hormonal syndrome
49
How do Ppomas and non-functioning pancreatic NETs usually present
asymptomatic resulting in Metastasis to liver
50
how do you manage Ppomas and non-functioning pancreatic NETs
surgery is controversial
* consider chance of mets (low chance of mets... surgical excision provides a better prognosis)
* 50-60% of surgery patients survive >5 years
* surgery can lead to many complications
51
What do MEN1 pituitary adenomas secrete
60% secrete prolactin
<25% secrete GH
5% secrete ACTH
10-20% are nonsecretory
52
what are the MC type of pituitary adenomas
>1cm aka macroadenomas
53
what is the clinical presentation of a pituitary adenoma secreting prolactin
female - galactorrhea, amenorrhea, and infertility
male - loss of libido, impotence, gynecomastia, infertility, galactorrhea
54
what is the clinical presentation of a pituitary adenoma secreting GH
acromegaly
55
what is the clinical presentation of a pituitary adenoma secreting ACTH
cushings disease
56
what are the clinical pesentations of nonsecretory pituitary adenomas
compressed pituitary tissue (hypopituitarism)
optic chiasm (visual disturbances)
57
what are lab evals of pituitary adenomas
"hypothalamic-pituitary testing based upon clinical presentation and suspected hormone hypersecretion - (see previously delivered material)"
58
what is management of pituitary adenomas
* selective transsphenoidal adenomectomy +/- radiotherapy for residual unresectable tumor tissue.
* medical treatment is same as non-MEN1 tumors
prolatinoma - cabergolin
excessive GH - ocreotide
excessive ACTH - pasireotide (somatostatin analog)
59
when is surgery indicated in adrenal adenomas
often they are non-functioning and benign so surgery only indicated if >4cm (red flag for malignancy)
60
what is a carcinoid tumor
a slow growing tumor of the bronchi, gastrointestinal tract, pancreas, or thymus
61
How do you treat carcinoid tumors
often they are asymptomatic until late in the disease but surgical excision is still recommended
62
what is a meningioma
tumor of the meninges - often asymptomatic
63
how do you manage a meningioma
refer to neurosurgery for surgical v nonsurgical treatment
64
what is a lipoma
tumor of adipose tissue
65
what is facial angiofibromas and collagenomas
tumors of fibrous or collagen tissues
66
what are the screening recommendations for MEN1 gene mutations
1. 2 or more MEN1 associated endocrine tumors
2. First degree relatives of an MEN 1 mutation carrier even if they are asymptomatic
67
what is the genetic testing for MEN 1
direct DNA testing for MEN1 gene mutations
68
what is the prognosis for MEN1
decreased life expectancy, with a 50% probability of death by age 50 years
69
what is MEN Type 2
a disorder characterized by a predisposition of medullary thyroid carcinoma (MTC), pheochromocytomas, and parathyroid tumors
70
what are the genetic mutations in MEN2
Genetic mutations in the RET proto-oncogenes
71
where is the RET gene expressed and what does it do
thyroid
parathyroid
adrenal glands
provides instruction for producing signaling protein within nerve cells.
72
what does a mutation of the RET gene lead to
excessive activation of signaling proteins resulting in tumor formation.
73
what are the 3 subtypes of MEN2
* MEN 2A (MTC, pheo, parathyroid)
* MEN2B (MTCH, pheo and other skeletal soft tissue presentations)
* familial medullary thyroid carcinoma (FMTCH)
74
what is the most common MEN 2 tumor
medullary thyroid carcinoma
(most common in both MEN2A and MEN2B, only feature in FMTC)
75
what occurs in MEN2 medullary thyroid carcinomas
malignant cells originate in the C cells of the thyroid and increase secretion of calcitonin
76
what is the clinical presentation of a medullary thyroid carcinoma
solitary thyroid nodule (75-90%)
cervical LAD (70%)
hoarseness/dysphagia (15%)
distant metastasis (5-10%)
77
what are the diagnostic studies used to diagnose medullary thyroid carcinomas
1. serum calcitonin (elevated with palpable nodule(s))
2. FNA biopsy
3. genetic testing for RET gene muation
4. PET scan if mets suspected.
78
whatere are mets found in medullary thyroid carcinomas
early mets - cervial lymph nodes
Late mets - mediastinal nodes, lung, liver, trachea, adrenal, esophagus, and bone
79
medullary thyroid carcinoma treatment
total thyroidectomy w lifetime supplemental thyroid hormone
80
If a patient has a + RET mutation but has no disease, what prophylactic treatment should be done
prophylactic total thyroidetomy
81
what should be avoided in MEN2 + RET patients
GLP-1 drugs such as ozempic
82
what is the difference between MET2 and non-MET2 pheochormocytomas
MET2 are 60-80% bilateral
non-MET2 are only 10% bilateral
83
how does a MET2 pheochromocytoma present
the same as a non-MET 2 pheochromocytoma: (4 P's)
palpitations
pounding headache
profuse diaphoresis
paroxysms lastig <1 hour
also presents with episodic or sustained HTN
84
how do you treat MEN2 pheochromocytomas
* complete resection of tumor is recommended by a skilled surgeon (remember BP must be <160/90 prior to surgery)
* use alpha adrenergic blockers at least 10-14 days prior to surgery
85
what are the alpha adrenergic blockers
doxasozin
prazosin
terazosin
86
if you have multiple MEN2 tumors that need to be removed, which one is ALWAYS removed first
pheochromocytomas
(im assuming because they make BP super labile during surgical procedurez)
87
How do MEN2 parathyroid tumors present
same as PHPT
"asymptomatic mild hypercalcemia with elevated PTH
remember hypercalcemia symptoms are stones, bones groans and moans"
88
what are diagnostics and treatment for MEN2 parathyroid tumors
same as MEN1 parathyroid tumors
"use CT/MRI, nuclear scan to confrim, also PTH levels and calcium levels
surgical removal
rsk of partial (3.5 glands) = risk of surgical failure
risk of total (all 4 glads w autotransplantation) = permanent hypoparathyroidism
oral cincalet (sensipar)
avoid thiazides and oral calcium"
89
what is marfanoid habitus and when would you see it
seen as a clinical presentation in MEN2B
characterized by:
high arched palate
pectus excavatum
bilateral pes cavus
scoliosis
90
what are neuromas and when are they seen
seen as a clinical presentation of MEN2B
growth of nerve tissue affecting eyelids, conjunctiva, nasal/laryngeal buccal mucosa, tongue and lips (hypertrophied lips)
91
when would you see intestinal autonomic ganglion dysfunction and how does it present
MEN2B
presents as chronic constipation
or complications of chronic constipation such as multiple diverticula and megacolon
92
what are the 5 groups that should be screened for MEN2/3
1. all patients with MTC (despite family hx)
2. all patients with MTC who has family hx of tumors
3. all patients with MTC and pheochromocytoma w/o family hx of MEN2
4. pts with BIL pheo
5. pts with unilateral pheo especially with elevated calcitonin.
basically:
if they have MTC or pheo at all, theyre getting screened
93
what is MEN type 4
a rare autosomal-dominant familial tumor syndrome caused by germline mutations in the gene CDKN1B¹
94
what types of tumors is MEN4 associated with
parathyroid
pituitary
pancreatic
but also:
adrenal
renal
testicular
neuroendocrine cervical carcinomas
and associated with ovarian failure
95
how do you manage MEN4 tumors
same as MEN1 tumors and non-MEN tumors
96
what are autoimmune polyendocrine syndromes (APS)
Rare immune endocrinopathies characterized by the coexistence of at least two endocrine gland insufficiencies that are based on autoimmune mechanisms.
97
what is the epidemiology of APS type 1
rare - 500 cases reported
higher freqeuncy in jews, sardinians, finns, norwegians and irish
98
pathology of APS type 1
Autosomal recessive disorder caused by mutations in the AIRE gene (autoimmune regulator gene) found on chromosome 21
99
what is the function of the AIRE gene
synthesizes a protein in the thymus called autoimmune regulator
autoimmune regulator protein helps T cells distinguis between self and foreign proteins and destroys autoimmune T cells
100
mutation of AIRE leads to what
autoimmune attack on teh body's tissues and organs
101
clinical presentation of APS type 1
Characterized by 2 out of 3 major endocrinopathies:
1. chornic mucotaneous candidiasis (most often 1st symptom in infancy)
2. acquired hypoparathyroidism (often 2nd clinical presentation years after 1st symptom)
3. adrenal failure (addisons)
102
besides the 3 characterizing endocrinopathies, what are other clinical presentations of APS 1
* Gonadal failure (MC - females)
* Poor dentition - (hypoplasia of dental enamel)
* DM-I
* Thyroid disease
* Alopecia, vitiligo
* Intestinal malabsorption, pernicious anemia
* Chronic hepatitis
* Nail dystrophy
* Debilitating diarrhea or obstipation
103
what are diagnostic evaluations of APS 1
* Antibodies to anti-interferon alpha and omega are identified in 100% of patients!
* genetic analysis showing AIRE gene mutation confirms diagnosis
104
how do you manage APS 1
* mucocutaneous candidiasis - ketoconazole
* replacement of hormones as needed (gonadal, thyroid, pancreas, adrenal)
* adrenal insufficiency treatment
105
what is APS 2
Dysfunction of human lymphocyte antigen (HLA) complex on chromosome 6 resulting in inability to make proteins that identify cells as "self"
106
what is the epidemiology of APS 2
* peak age of 20-60
* more common in female
* usually has strong fam hx of multiple autoimmune disorders.
107
what is the etiology of APS 2
unknown, but thought to be a combo of genetic and environemntal factors
108
what is the clinical presentation of APS 2
characterized by 2+ of the following:
1. primary adrenal failure (addisons)
2. autoimmune thyroid disease
3. type 1 diabetes
4. primary hypogonadism
109
what are other conditions that could present with APS 2
* celiac
* myasthenia gravis
* vitiligo
* alopecia
* serositis
* pernicious anemia
110
what are diagnostics for APS 2
* Diagnosis of each individual condition is based upon typical clinical presentation and laboratory diagnostics
* No specific genetic test to confirm dx
111
what must be monitored in APS 2
every 1-3 years screen for MC abnormalities:
* Comprehensive H&P
* CBC, metabolic panel, TSH, and vitamin B12 levels
