Endo 2 Treatments and Diagnosis Flashcards
Lab findings of hypoglycemia, ↑ LFTs, or CPK
(creatine phosphokinase)
Genetic testing - confirmatory
Complication → AKI
Tx:
Avoid hypoglycemia
Enzyme replacement therapy
Tx of complications
Fructosemia D&T
Genetic testing - confirmatory
Management: complete avoidance of fructose and sucrose
Galactosemia Dx
GALT enzyme def included in newborn
screening (WV)
RBC galactose-1-phosphate: ↑ in GALT def
GALT enzyme activity - ↓ in GALT def
Galactosemia Tx
Minimize dairy galactose
d/c breastfeeding/formulas
Use soy-based formulas (Alsoy, Isomil ProSobee)
Later avoid dairy products
Amino Acid Disorders Dx & Tx
Dx
Newborn screening (all states)
↑ plasma phenylalanine
Tx
* Dietary restriction of phenylalanine (avoid meat, dairy, nuts, aspartame)
* Supplement tyrosine
* Sapropterin (Kurvan) - adults/peds - activates PAH to promote breakdown of phenylalanine
* (only use if pt still as enzyme)
* Pegvalisale (Palyniq) - adults ONLY - degrades phenylalanine
like peg adults only- degrades like bdsmn lannisters
sap-rope-turn like a funnel cake is sticky like sap and twisty
Maple Syrup Disease D&T
Dx: Newborn screening
Prenatal screening
Tx:
* Dietary management - strict protein restriction
* Medical grade formula/food; Trial of thiamine supplement - 4wks
* Control metabolic decomposition: lower BCAA levels via hemodialysis
* Inhib further protein catab and enhance protein synth: d/c protein intake x 24-48hrs
* IV glucose - provides calories (prevents protein catab for energy)
* IV insulin if glucose is > 130mg/dL - insulin enhances endogenous protein synth
* Liver transplant - last resort
Homocystinuria Dx and Tx
Dx:
Newborn screening - ALL states
↑ homocysteine and methionine in plasma of urine
Tx:
* Dietary modification - protein restriction
* Vitamin B6, B12, folate supplements (helps convert homocysteine → methionine)
* Supplement cysteine
* Betaine (Cystadane) - helps convert
* homocysteine → methionine
be tame for home w mom
Types of glucosphinolipids
part of cell wall. protect from degrading enzymes
Types of glycosphingolipids:
Gangliosides - Tay-Sachs Dz
Cerebrosides - Gaucher Dz
Globotriaosylceramide - Fabry Dz
Sphingomyelin - Niemann-pick Dz
Gaucher Disease Dx
Newborn screening (handful of states)
Low beta-glucosidase leukocyte enzyme activity
Genetic testing - confirmatory:
Rec in Ashkenazi Jews
Prenatal testing possible
Gaucher Disease tx
Enzyme-replacement therapy (ERT) w/
recombinant glucocerebroside (Imiglucerase)
Helps breakdown glucocerebroside
NOT effective in ↓ CNS s/s
Substrate-reduction therapy (SRT):
Blocks prod of glucocerebroside
Eliglustat (Cerdelga) and miglustat (Zavesca)
a gausher surrounded can an igloo
Tay Sachs Disease Dx and Tx
Dx
* Genetic counseling
* Newborn screening (WV), pregnancy screening
* Hex A enzyme analysis - low level
Tx
Supportive care
s/s control
Manage inf
Prevent complications → OT, feeding tube
Prevention:
Carrier screening, genetic counseling (esp
Ashkenazi Jews, French-Canadians, Cajuns)
Emerging - Hex A enzyme replacement tx,
substrate reduction tx
Fabry Disease Dx and Tx
Dx
* GLA enzyme activity ↓
* Confirm w/ genetic testing
Tx
* Enzyme-replacement - cornerstone of tx
* Agalsidase beta (Fabrazyme)
* Chaperone tx - migalastat (Galafold)
MOA: ↑ GLA enzyme activity preventing
accumulation of GL3 (adults ONLY)
Control neuropathic pain
Stroke prevention (ASA + Clopidogrel, antiHTN, statins)
A gal said my gala stat needs a chaperone. fairies have gallas
Niemann-pick disease Dx and Tx
Dx
* Newborn screening (NOT in WV)
* Genetic testing
Tx
* ERT for NPD Type B - olipudase alfa-rpcp (Xenpozyme)
* NO ERT is FDA-approved for Type A or C
* Supportive care - PT/OT, feeding tube
- O2 tx and blood transfusion; avoid contact sports if splenomegaly
play with pudding in the tub
Pompe Disease Dx and Tx
Dx:
* Newborn screening (NOT in WV)
* Acid α-glucoside (GAA) levels ↓
* Genetic testing confirms dx
* Prenatal screening
Tx
* Enzyme replacement therapy - alglucosid- α (Lumizyme)
* Monitor - risk of gradual weakness, fractures, dysphagia, sleep apnea
alglucosid-a = algorythm cheer speech
Hyperphosphatemia tx only
- Acute severe dz - IV fluids if no CKD
- Hemodialysis if CKD
- Mild dz - dietary restrictions (avoid dairy, meats, beans)
Mod-severe - phosphate binders:
* Calcium acetate (PhosLo)
* Lanthanum carbonate ( Fosrenol)
* Sevelamer (Renagel)
Hypophosphatemia tx
Treat underlying disorders
- Avg pt req 1-2g of phosphate per day for 7-10days to replenish body stores
- Mild hypoP - ↑ dietary phosphate intake (dairy, meats, beans)
- Mod-severe hypoP - phosphate supplement (Na or K Phosphate)
1g/d for a week.
mild fix with diet
severe fix with supplement
Phosphorus supplement
Na or K phosphate in capsule or liquid
AE: weakness, N/V/D, abd pain, brady,arrhythmia
CI: hyperP, severe renal imp, hyperK
Safe in pregnancy
Hypomagnesemia tx
↑ dietary Mg - dark green veggies, legumes (beans/peas), nuts, seeds, whole, unrefined grains
Pharm replacement:
Severe (tetany, arrhythmias) - 50mEq of IV Magnesium
Mild-Mod - PO Magnesium
Replenish Ca and K if indicated
Phosphate binders
indicates in ESRD on dialysis
when you have too much phosphorus and you need to get rid of it
Paget Disease Dx Tx
Dx
* * ↑ alkaline phosphate and bone-specific
* alkaline phosphate (BSAP)
* XRAY:
* Early dz - lytic lesion
* Later dz - lytic lesions and excessive bone formation
* Radionucleotide bone scan - determines extent of dz
Tx
* Bisphosphates - inhib osteoclast activity
* Alendronate (Fosamax)
* ibandronate (Boniva)
* risedronate (Actonel)
* zoledronic acid (Reclast)
* NSAIDs for joint pain
* Ca and Vit. D supplement
Men 1 wermer syndrome
Management
Sx removal: controversial btw partial and total parathyroidectomy:
Partial: 3 1⁄2 glands removed → Risk of sx failure
Total: all 4 glands w/wo autotransplantation → Risk of permanent hypoparathyroidism
Surgical failure and recurrence rates are high
Ectopic parathyroid tissue is common
Hypercalcemia - nonsurgical treatment
Oral cinacalcet (Sensipar)
Avoid oral calcium and thiazide diuretics
Gastrinoma Labs and Dx
Fasting serum gastrin:
> 150 pg/mL is ind; >1000 pg/mL is diagnostic
Secretin stimulation test:
(+) - serum gastrin levels post admin >120 pg/mL
over baseline levels
D/C PPI 6d prior and H2 blocker 1d prior to
testing → otherwise false positive results
Convert PPI to H2 therapy in appropriate pts
PPI - Omeprazole
Gastrinoma Management
Conservative tx is rec:
Long-term high-dose (PPI) +/- histamine 2-R antagonist
omeprazole (Prilosec) or esomeprazole (Nexium)
+/- cimetidine (Tagamet), famotidine (Pepcid)
Treat hypercalcemia
Sx is controversial
Most often rec to prevent liver metastasis
Insulinomas Dx
72-hr fast: most reliable test
Req hospital adm
Additional testing during fast:
[Plasma insulin] - ↑
C-peptide levels - ↑
Insulinoma Management
Sx removal is rec
Meds while waiting for sx or if CI to sx:
Freq carb intake
PO diazoxide (Proglycan) - K+ channel activator - inhibits secr of insulin
Everolimus (Afinitor) - antitumor agent that induces insulin resisitance
Glucagonoma Labs, Dx, Tx
Labs and Dx:
↑ BG
↑ fasting blood glucagon level > 150 pg/mL
Management:
Control BG
Octreotide - inhibits glucagon and insulin
Rec if single lesion is localized at time of dx
VIPoma-rare dxtx
Dx:
[serum VIP] > 75 pg/mL; confirm w/ repeat
Management:
Correct fluid, electrolyte, and vitamin imbalances
octreotide - inhibits VIP - helps control D
Sx excision of primary tumor, if no mets at diagnosis
Pancreatic polypeptie secreting tumors and non functioning pancreatic nets
MC - macroadenomas (>1 cm)
Management:
Selective transsphenoidal adenomectomy
+/- RT
Medical tx is the same as non-MEN1 tumors:
PRLoma - DA agonist
Excessive GH - octreotide - ↓ GH secr
Excessive ACTH - pasireotide (Signifor) -
inhibits ACTH secr
MEN1 other tumor
Meningioma
Tumor of the meninges - often asympt
Refer to neurosurgeon for sx vs non-sx mgmt
Adrenal adenoma
Often non-fxnal and benign
Sx is only indicated if > 4 cm
Carcinoid tumor
Slow-growing tumor of the bronchi, GI tract,
pancreas, or thymus
Asympt until late in dz
Sx excision is recommended
MEN1 screening
Gene mutation screening rec:
≥ 2 MEN1 assoc endo tumors
1st degree relatives w/ MEN1 mutation carrier even if asympt
Genetic testing:
Direct DNA testing for MEN1 gene mutations
Prognosis:
↓ life expectancy w/ a 50% probability of death by 50y/o
Medullary Thyroid Carcinoma Dx
Dx:
Serum calcitonin - ↑ w/ palpable nodule FNA biopsy
Genetic testing for RET gene mutation
PET scan if mets is suspected
Early mets - cervical lymph nodes
Late mets - mediastinal nodes, lung, liver, trachea,
adrenal, esophagus, and bone
Medullary Thryoid Carcinoma Tx
Treatment:
Total thyroidectomy followed by lifetime
supplemental thyroid hormone
Prophylactic total thyroidectomy should be
offered to patients with (+)RET mutation w/o disease
Avoid GLP-1 drugs
Pheo Labs and Tx
Dx-
Plasma free metanephrines
Urine-fractionated metanephrines and creatinine
Clonidine suppression testing
Non-contrast CT of adrenal gland
PET scan - r/o malignancy
Tx-
Sx resection
α-blockade at least 10-14d prior to Sx
Pheos need to be removed prior to any other
surgical procedures of MEN2 pts
Parathyroid tumors dx tx
Confirm tumor location w/ parathyroid nuclear scan
Management:
Sx removal: controversial btw partial and total parathyroidectomy:
Partial: 3 1⁄2 glands removed → Risk of sx failure
Total: all 4 glands w/wo autotransplantation → Risk of permanent hypoparathyroidism
Hypercalcemia - nonsurgical treatment
Oral cinacalcet (Sensipar)
Avoid oral calcium and thiazide diuretics
MEN2 screening
MEN2 Screening Rec - RET mutation:
All pts w/ MTC (despite FMHx)
d/t de novo germline RET mutation
Patients w/ bilat pheo or unilat pheo (esp w/ increased calcitonin levels)
MEN4
Management - similar to MEN1 tumors as well on individual non-MEN tumor management recommendations
Autoimmune polyendocrine syndromes
Polyglandular AI (PGA) Sundromes - rare immune endocrinopathies characterized by the
coexistence of ≥ 2 endocrine gland insufficiencies that are based on AI mechanisms
Autoimmune polyendocrine syndrome Type 1
juvenile
Dx:
* Based on presentation and lab diagnostics
* 2 out of the 3 endocrinopathies confirmed on testing
- Genetic analysis - AIRE gene mutations
- confirm diagnosis
- Antibodies to anti-interferon alpha and omega can be identified in 100% of patients
Tx:
* Mucocutaneous candidiasis - ketoconazole
- Replacement of minerals/hormones as needed - calcium (parathyroid), thyroid, gonadal, adrenal
- Increased risk of acute Addisonian crisis when initiating treatment of assoc endocrinopathies
- (ensure patients are appropriately treated for adrenal insuff before treating other conditions)
APS type 2
Dysfxn of human lymphocyte antigen (HLA) complex on chromosome 6
HLA allows immune system to recognize as self
Dx
No specific genetic test to confirm dx
clinical diagnosis
Tx-
Individual disease component tx:
Graves dz- radioactive iodine, antithyroid medications, surgery
Hormone replacement - thyroid, gonadal, adrenal
Increased risk of acute Addisonian crisis when initiating treatment of associated endocrinopathies
(ensure patients are appropriately treated for adrenal insufficiency before treating other conditions)
Monitoring APS Type 2
Dx:
Based on typical presentation and lab diagnostics
No specific genetic test to confirm dx
Monitoring:
Every 1-3yrs- screen for MC abnormalities
Comprehensive H&P CBC, metabolic panel, TSH, and vitamin B12 levels
Dx Precocious Puberty
assess bone age - Xray
Step 1: Initial Laboratory Evaluation
Serum testosterone - ↑ in all cases
Serum LH and FSH levels - ↑ in CPP
low/normal in peripheral causes
Step 2: Confirm CPP from peripheral etiologies:
Indication - LH/FSH are borderline high ULN
GnRH-analogue stimulation test:
Rx: leuprolide - stimulates the anterior pituitary to release LH/FSH
Results:
↑ in LH indicates CPP
No rise in LH = peripheral etiology
Step 3: Look for peripheral source:
Serum hCG - ↑ in hCG tumor
DHEA - ↑ in CAH and adrenal tumors
17α-hydroxyprogesterone - ↑ in CAH
Genetic testing if concern for LH/Gsα mutations or if presentation is consistent with MAS
Step 4:
MRI to r/o CNS lesion w/ CPP or ↑ hCG
OR
CT chest/abd - r/o hCG tumor of the
mediastinum, liver, or peritoneum or
androgen-secreting adrenal tumor
OR
Testicular US - r/o Leydig-cell tumor
Precocious Puberty Tx - CPP
Treat underlying cause if known (CNS tumor)
Idiopathic CPP: long-acting GnRH agonists - Leuprolide acetate
MOA - chronic stimulation of the GnRH-R in pituitary → desensitization of the R and ↓ LH/FSH
Initial stimulation ↑ LH/FSH and sex steroid prod
Prolonged stimulation ↓ LH/FSH to prepubertal levels
Effects:
Stops early pubertal development
delays bone maturation prevents early
epiphyseal closure → ↑ final height
Monitor: halting of s/s, suppression of
LH/FSH/testosterone (puberty resumes after d/c of med)
Precocious Puberty - Peripheral
Tumors - surgical removal
Exogenous steroids - identify and remove source
CAH - suppress androgen prod w/ glucocorticoids
McCune-Albright syndrome and familial male-limited precocious puberty:
Androgen-R antagonist (spironolactone) + aromatase inhibitors [anastrozole (Arimidex)] - blocks conversion of testosterone to estradiol
Alt: Steroid synthesis inhibitor - ketoconazole - req high dosing leading to a risk of hepatotoxicity
Goal: halt further sexual development and prevent premature closure of the epiphyseal plates
Delayed Puberty Dx
XRAY - bone age
Bone age delayed and growth velocity is normal
→ CDGP
Serum testosterone - low for age
Gonadotropins:
LH/FSH ↑ - primary hypogonadism or gonadal
failure
LH/FSH ↓ - secondary hypogonadism
Delayed puberty Management
Presumed congenital delay of growth and puberty (CDGP):
Reassurance with f/u vs. testosterone therapy
Consider testosterone if pt’s self-esteem is affected d/t stature and/or prepubertal appearance
Testosterone replacement therapy:
Secondary hypogonadism - interrupted therapy after 6mo to determine if endogenous LH and FSH secretion has ensued
Primary hypogonadism - indefinite therapy
+/- aromatase inhibitor → greater final adult height
T indications
Testosterone therapy indications:
Lack of puberty onset by 14y/o
Primary testicular failure (hypergonadotropic hypogonadism)
Severe hypogonadotropic hypogonadism of any etiology w/ serum testosterone levels < 150 ng/mL
Age-related hypogonadism
Condition Definition
Age related hypogonadism
Hypogonadal testing should be utilized ONLY
when symptoms are present
ONLY rec if at ≥ 3 s/s of androgen def w/ testosterone levels <200 ng/dL and benefits outweigh risk
S/S: ED, poor morning erection, ↓ libido, depression, fatigue, and inability to perform vigorous activity
Goal of therapy: maintenance of secondary sexual characteristics; ↑ libido; improved muscle strength, fat-free mass, and bone density
Gynecomastia - mass
Malignancy will be unilateral, non-tender, and offset from areola
Observe x 3 mo for regression
If no regression begin 9-12mo of med therapy:
Selective estrogen-R modulator (tamoxifen)
Aromatase inhibitor - anastrozole (Arimidex)
Sx for persistent or severe s/s > 12mo
Gynecomastia - breasts tender
Neonatal - reassurance, no intervention
Pubertal - reassurance - s/s resolve w/i 1-2 yr
Drug-induced - d/c therapy and monitor for improvement of s/s
Androgen deficiency - testosterone therapy
hCG tumor - imaging (CT/MRI) and refer to general surgeon
Goals Testosterone
Restore testosterone levels, Dev and maintain secondary sexual characteristics and normal sexual fxn, Build and sustain normal bone and muscle mass, Assist in
the proper psychosocial adjustment of adolescents w/ hypogonadism
Test management
- Eval pt 3-6mo after tx initiation, then annually
- Monitory testosterone levels 3-6mo after initiation of tx
- Check hematocrit (CBC) before starting, at 3-6mo, then annually
- If hematocrit is > 54% stop tx until it is decreased → eval pt for hypoxia and OSA
- Measure bone mineral density of lumbar spine/femoral neck after 1-2yrs of tx in hypogonadal men w/ osteoporosis
Men ≥ 40y/o w/ baseline PSA > 0.6ng/mL, perform a digital rectal exam and check PSA
before initiating tx, then at 3-6mo
Test CI and guidelines
CI: metastatic prostate CA, breast CA
Caution w/ undiagnosed prostate nodule or induration, PSA > 4ng/mL,
erythrocytosis (hematocrit > 50%), severe urinary tract s/s assoc w/ benign prostatic hypertrophy, uncontrolled CHF
Guidelines:
Avoid testosterone replacement in pts w/ mild vague s/s and borderline/low testosterone on occasion
Trial tx should be avoided
Testosterone therapy suppresses pituitary-testicular axis, spermatogenesis, and ↓ testicular
