MEN (multiple endocrine neoplasia) and DM type I
A type I could die from ----- despite severe hyperglycemia within days without insulin treatment
"starvation"
What is the precursor to the production of insulin?
C-peptide
How is MEN 2B diagnosed?
Clinically by the presence of early-onset MTC and extra endocrine manifestations -ganglioneuromas of the lips, tongue, and colon -distinctive facies with enlarged lips -"marfanoid" body habitus
What is Virilization?
Development of male physical characteristics in women -muscle development -Deep voice -male pattern baldness -worsened hirsutism
What is MEN type II? Men 2A? Men 2B?
Mutations in RET proto-oncogene MEN 2A: Familial medullary thyroid carcinoma MEN 2B: Medullary thyroid carcinoma + pheochromocytoma
Explain Octreotide scan VS Ga-DOTATATE PET scan
Octreotide: --somatostatin receptor scintigraphy --non-invasive test use to evaluate the body for presence of neuroendocrine tumor cells GA-DOTATATE PET scan: --SUPERIOR= more tumors found -test is performed in a nuclear medicine department
What are some signs/symptoms of DKA?
Polydipsia, polyuria, malaise -weakness -nausea and vomiting -missed insulin injections -possible decreased perspiration -possibly fever -chills -SOB -acute chest pain -abdominal tenderness
If ketones are present in the urine?
Present to ER for further eval and avoid Diabetic ketoacidosis
FMTC is diagnosed in families with --- or more cases of MTC (medullary thyroid carcinoma) in the absence of pheochromocytoma or parathyroid adenoma/hyperplasia
four or more
What is the treatment for Carcinoid syndrome?
Somatostatin analogs
What is the treatment for a gastrinoma?
Surgery: Whipple Pancreaticoduodenectomy for large, advance tumors Also PPI for lower gastric hyperacidity (give 4x usual dose)
What is Gluconeogenesis?
metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol or glycogenic amino acids. It is another mechanism to keep glucose from dropping too low besides glycogenolysis
Individuals who have FMTC will have
multiple family members who are affected as well
What is MEN type I
mutations in MEN 1 tumor suppressor gene (protein called meningitis)
The major of de novo pathogenic mutations (MEN-2B) are ---- in origin
paternal
A child with a random glucose of >170
red flag for type I DM
Explain GEP-NETs in GI tract?
-60% are non-secretory or non functioning -can still present with weight loss, abd pain or jaundice -40% are functional
What causes DKA?
-Absolute insulin deficiency -combined with counter regulatory hormone excess -dehydration -acid-base abnormality
What are some rare causes of Hirsutism and Virilization?
-Acromegaly -ACTH-incduced cushing syndrome -Meds: minoxidil, cyclosporine, phenytoin, anabolic steroids, interferon
What is the treatment for Profound Hyperglycemia? Acute illness
treat with insulin
What is the starting dose of basal insulin for Type I diabetic adult?
10 units
Never make more than a --- change in insulin doses at one time
10-20% change
A mass will be diagnosed as an ovarian neoplasm IF
1: Serum testosterone is >2 OR 2: serum testosterone is >2.5 fold the normal
All carcinoid tumors...
Affect cells that make hormones; originate in stem cells in gut wall; appendix can contain carcinoid tumor -grow slowly but can metastasize
In type I DM, the ---- cells are still working, but the ---- are not
Alpha cells are still working Beta cells are not, they have been destroyed
With Virilization, there is a higher incidence of -----?
Androgen-producing neoplasm
MEN is a ----- inheritance
Autosomal dominant inheritance
1 out of 5 pts that have a gastrinoma also have?
MEN-1
What kind of testing should be done for carcinoid tumors?
-Can try to measure biogenic amine levels --serotonin --5-HIAA --Chromographin-A --Catecholamines -CT, MRI, Endoscopic ultrasound -PET scans
What is Carcinoid syndrome?
-Caused by secretion of serotonin and other neuropeptides into systemic circulation -Episodic flushing, diarrhea, and eventual right sided valvular heart disease
What is TYPE II dm?
-Chonic obesity, inactivity, and other lifestyle factors lead to increased levels of fatty acids and inflammation, leading progressive decrease sensitivity of cellular insulin receptor sits "insulin resistance" causing increase serum glucose levels
What might you see on PE for type I DM?
-Dehydration -Hypotension -Kussmaul breathing (deep, rapid breathing) -neuropathy
What is the treatment for type I DM?
-Exogenous Insulin -Diet moderation -Frequent blood sugar monitoring
What is the treatment of DKA?
-Fluids -Insulin -Electrolytes -Correction of acid-base -tx infection if needed
What labs would you do for a glucagonoma?
-Glucagon in blood >1000 -Fasting glucose to detect diabetes -Consider MEN 1 -CT scan and MRI best imaging - usually >5cm
What are some symptoms and signs of PCOS?
-High growth on chin, upper lip, abd, chest -Sebaceous gland-acne -menstural irregularities -Anovulation; amennorhea -Frontal blading
Total testosterone >200 OR Free testosterone >40 can indicate?
-Hirsutism and virilization
What are some imaging/testing you can do for a gastrinoma?
-Imaging: Somatostatin receptor scintigraphy- find primary tumor and metastases -Endoscopic ultrasonography for primary tumor -CT scanning; MRI to detect liver metastaes
What does Ketosis (in DKA) result from?
-Increase in free fatty acid release from adipocytes -resulting in shift-ketone body synthesis in the liver -Ketone bodies neutralized by bicarbonate -as bicarbonate stores as depleted --metabolic acidosis begins
What causes dehydration in a TYPE I diabetic?
-Increased levels of glucose, cause osmosis from cells= leading to dehydration
What is Gestational DM?
-Insulin resistance caused by placental hormones, such as prolactin, cortisol. Insulin resistance resolves with delivery. GDM is a risk factor for developing type II DM
If someone inherits the MEN, then
-It occurs more commonly in younger individuals -tumors may be multifocal -tumors are more aggressive and recur more frequently
Explain TYPE I DM
-Mostly children 4-7 and 10-14 -not related to family history -studies to determine direct cause still under investigation -occurs from autoimmune related beta cell destruction -can progress over days to weeks in children -slower progression in adults (weeks to months)
What are the 3 Ps (organs involved) in MEN-1?
-Parathyroid -Pancreas -Pituitary
What is commonly affected in MEN-4?
-Parathyroid ~95% -pancreas ~25% -Pituitary ~10%
Explain PCOS?
-Polycystic Ovary Syndrome -50% of all cases of Hirsutism -Elavted serum testosterone -Familial --Androgen excess --Ovarain dysfunction --Absence of other causes -Will also see --high levels of serum insulin --acne, hair growth, male pattern balding
What are the signs of diabetes (type I)
-Polyuria, increased thirst -Polyphagia with weight loss -Fatigue and weakness -Possible muscle cramps -Enuresis in young children -Blurred vision -nauses a -fruity (ketone) breath oder
What will you find in most TYPE I DM pts?
-Positive for islet-directed autoimmunity -GAD-65 antibody and anti-insulin antibodies are commonly tested to confirm within 6 months of diagnosis
Explain Glucagonomas?
-RARE, NET, usually malignant -large intrapancreatic tumor; pancreatic islet cell tumor -60% have mets to liver -secretes glucagon and can secrete gastrin too
What is the treatment for hirsutism and virilization?
-Resect androgenizing tumors of ovary or adrenal gland -stop any drugs causing -laser or topical treatment for hair -Oral contraceptives if no contraindications -Spironolactone -Metformin (in PCOS pts) -GnTH agonist (for postmenopausal women)
Explain a Gastrinoma
-Secrete excessive hormone= gastrin -1/2 found in duodenum -1/4 in pancreas -1/10 in lymph nodes -50% are malignant and will spread to the liver
What is the treatment for a carcinoid tumor?
-Surgical excision if possible; Chemo -Ocretotide will only decrease the symptoms
What are the 3 types of diabetes?
-Type 1 -Type 2 -Gestational DM
What are the signs and symptoms of Glucagonoma?
-Wight loss (DM in 35%) -Diarrhea -Nausea -Peptic ulcer -Necrolytic migratory erythema (glucagonoma syndrome)
How is MEN 2A diagnosed? What does it affect?
-clinically by the occurrence of two or more specific endocrine tumors in a single individual or in close relatives
What is Glycogenolysis?
-conversion of glycogen to glucose. The hormones glucagon and epinephrine stimulate glycogenolysis
What are the physical findings/labs of DKA?
-dry skin -labored respirations (kissmauls) -dry mucous membranes -decreased skin turgor -decreased reflexes -tachycardia -hypotension -confusion -abd pain -Glucose >300 Bicarb less than 15 Ph <7.30 -ketonemia and ketonuria
Explain what an Insulinoma is?
-most common form of GEP-NET -Small, inside HEAD of pancreas --90% are benign -Secretes increased insulin
What is the treatment for Profound Hypoglycemia?
-oral fast-acting carbohydrates, IV dextrose
Explain neuroendocrine tumors
-originate in endocrine glands or enterochormffin-like cells (GI and PULM) -RARE neoplasms that being in neuroendocrine cells -secrete hormones -benign form
What is Type I diabetes?
-result of interactions of genetic, environmental and immunologic factors that ultimately lead to the destruction of the pancreatic beta cells and complete insulin deficiency
A1C and blood sugar averages 6.0 7.0 8.0 9.0 10.0 11.0 12.0
6.0= 126 7.0= 154 8.0= 183 9.0= 212 10.0=240 11.0= 269 12.0= 298
What are some signs and symptoms of insulinomas? <54mg/dL <50 mg/dL <45 mg/dL
<54= elevated HR, palpitations, sweating, shaking , nausea, hunger <50= irritability, confusion, blurred vision, difficulty speaking <45= loss of consciousness, seizure
-If a pt has a fasting gastrin level of >1,000, suspect?
Gastrinoma
What is Insulin?
A hormone secreted by the pancreatic beta cells in response to increased serum glucose levels. Insulin is critical to enabling glucose to be transport into the cell and reducing serum glucose
What is Glucagon?
A polypeptide hormone secreted by the alpha cells of the islets of langerhans in response to hypoglycemia, which stimulate glycogenolysis in the liver
In what type DM do you see Beta cell destruction by immune mediation?
Type I, it is autoimmune
What is the goal of DKA treatment?
BG 150-250 and acidosis resolved
What is essential for type I diabetes
Basal insulin
What is FMTC?
Familial medullary thyroid carcinoma -MEN 2
What is the leading cause of death in MEN-1?
Functional endocrine tumors of the pancreas
Explain GLUT 1-4 (the glucose transporters)
GLUT 1: Blood, blood brain barrier, heart --insulin dependent GLUT 2: Liver, pancreas, small intestine --insulin independent, high K, low affinity GLUT 3: Brain, neurons, sperm --Insulin independent, low K, high affinity GLUT 4: Skeletal muscle, adipose tissue, heart
Glucagon will ---- blood sugar, while Insulin will ---- blood sugar.
Glucagon= increase Insulin= decreases blood sugar
What is the treatment for a postmenopausal women, with severe ovarian hyperandrogegism, and an oophorectomy is contraindicated?
GnTH agonist (lupron)
DO you see a higher glucose in DKA or Hyperglycemia Hyperosomolar syndrome?
HHS! (can be 600-1200)
What is the best imaging and treatment for an Insulinoma?
Imaging: GA-DOTATATE_PET (best imaging: nuclear scan) Tx: Excision or Ocreotide
What is MEN-4?
Inactivation of the cyclin dependent kinase inhibitor 1B (CDKN1B) tumor suppressor gene
What is MEN?
Its a cancer, that produces hormones that will mimic the pituitary gland
What is the scary part about an Insulinoma?
Leads to severe, life-threatening fasting hypoglycemia
What will you with C peptide in Type I DM?
Low to no detectable C-peptide levels -thus C-peptide can be tested to assess for type I DM
What can carcinoid tumors involve?
Lungs, thymus, liver, pancreas, ovaries, prostate, and kidneys
If glucose is >150 what is the recommendation for insulin?
Meal dose + correction dose
What is most commonly affected by MEN 2A, and virtually develops in all cases?
Medullary thyroid carcinoma
What is more common, MEN 2A or 2B?
Men 2A (70-80% of MEN 2 cases)
What is the Whipple procedure?
Removal of head and neck of pancreas, proximal duodenum, and gallbladder Tx: pancreatic carcinoma
What is the treatment for Glucagonoma?
Resection is the only curative treatment -Control symptoms with somastatin analogs -chemo can help if widespread metastases
Who is more insulin sensitive, TYPE I or II?
TYPE I
If there is NO abnormality found on a lipid panel, then...what should be suspected?
TYPE I DM should be suspected
What is Hirsutism?
Terminal hair growth that appears in women in a male pattern -Can be idiopathic or familial --PCOS, ovarian hyperthecosis, acromegaly, ACTH-induced Cushings
How can you diagnose/confirm the presence of MEN-4?
Testing for CDKN1B mutations
What can MEN 2A AFFECT?
Thyroid Adrenal Medulla Parathyroid
Does DKA occur more often in Type I or Type II DM?
Type I
random blood sugar of >200, with signs of polyuria, increased thirst and fatigue
Type I DM
Gastrinomas lead to what syndrome?
Zollinger-Ellison syndrome
Excess gastrin secretion can lead to? And what else?
Zollinger-Ellison syndrome -Also (gastrin stimulates acid secretion) --Peptic ulcer disease ---abd pain, heart burn, GI bleed, weight loss
Basal insulin is based on
body mass
Even if C-peptide is low or undetectable, it MUST be paired with ------to be useful in diagnosis
elevated glucose level
Carcinoid tumors originate ---- or ----- secrete serotonin and may metastasize
intestine or lung
If blood glucose is staying >300, or if nausea and vomiting, then ---- should be measured?
ketones in urine should be measured
