Endocrinology Exam 2 Cards Flashcards
Role of FSH
Stimulates Sertoli cells to regulate spermatogenesis and produce inhibin B to cause negative feedback
Role of LH
Stimulates testosterone synthesis in the Leydig cells of the testes, testosterone give negative feedback and encourages spermatogenesis
2 things that testosterone can be converted into
DHT dihydrotestosterone) and Estradiol
2 proteins that bind systemic testosterone
Sex-hormone binding globulin
Hepatic metabolism, Renal excretion
Adrenarche
At 6-8 years of age - the zona reticularis produces greater amounts of androgens
Gonadarche
Around age 9 - activation of the HPG axis occurs allowing for the production of GnRH, LH, FSH, and Testosterone
Tanner stages
5 stages of male sexual characteristic development
Begins with testicular growth and sparse pubic hair, followed by phallic growth (length then width) and thicker pubic hair as the testes continue to grow
Measuring tool for testicular size
Prader orchidometer
Prepubertal
Pubertal
and
Adult
Testicular sizes
Prepubertal - 1-3mL
Pubertal - 4-12 mL
Adult - 12-25 mL
Greater than 2.5 cm long = Puberty
Precocious male puberty
Evidence of puberty in boys under the age of 9
Isosexual precocious puberty
Premature development of APPROPRIATE characteristics
Heterosexual precocious puberty
Development of secondary sexual characteristics of the opposite sex
Precocious puberty that results from premature release of GnRH
Gonadotropin dependent or central precocious puberty
Precocious puberty that results from increased secretion of androgens from the testes of adrenal cortex
Gonadotropin independent or peripheral precocious puberty
Cause of central precocious puberty
Often a CNS lesion or idiopathic - need to do a neurologic workup
3 things that may cause peripheral precocious puberty
hCG secreting tumor
Adrenal androgen secreting tumor
Congenital Adrenal hyperplasia
2 enzymes usually deficient in CAH
21 hydroxylase and 11beta hydroxylase
McCune-Albright syndrome
Acquired mutation of the Gsalpha subunit resulting in steroidogenesis
More common in females
McCune-Albright syndrome triad
Bone dysplasia
Cafe-au-lait skin pigmentation
Precocious puberty
Can be associated with stimulation of other endocrine systems
Familial male limited precocious puberty
Autosomal dominant disorder caused by LH receptor mutations
Non-biologic source of peripheral precocious puberty
Exposure to exogenous androgens such as testosterone creams, etc.
5 historical things to know for a precocious puberty patient
Onset, Progression, Associated symptoms (Neuro), Exposures, When family members went through puberty
Physical exam difference between central and peripheral precocious puberty
Central - Enlarged testicles
Peripheral - Testicles remain small
Testicular tumor presentation
Asymmetrical enlargement
Bone age assesment for precocious male puberty
X-ray of the left wrist and hand
Assesment of bone age X-ray and other measurements of PP
Compare data over six months rapid growth indicates a central or peripheral problem, slow growth is often more benign
Initial lab tests for precocious puberty (3)
Serum testosterone
LH and FSH (elevated in central, low in peripheral)
Lab to detect and hCG tumor
Serum hCG
2 Labs to detect CAH
DHEA (also could be adrenal tumor) and 17a-hydroxyprogesterone
Lab test that distinguishes CPP from peripheral
GnRH stimulation test
GnRH stimulation test interpretation
LH rise = CPP
No LH rise = Peripheral
3 places an hCG secreting tumor might be located with imaging modalities for each
Brain (MRI), Abdomen (CT), Testicles (US)
Central precocious puberty management
Refer tumor to neurosurgery
Use long acting GnRH agonists
How do long acting GnRH agonists help with central precocious puberty
GnRH agonists lead to desensitization of receptors and lower secretion of LH and FSH
2 GnRH agonist options
Histrelin acetate SQ implant
Leuprolide IM 1,3, or 6 month formulations
Treatment for peripheral precocious puberty
Depends on source:
Surgery for tumors. Androgen suppression for CAH
Goal is to halt sexual development and premature epiphyseal plate closure
Steroid synthesis inhibitor for precocious male puberty
Ketoconazole at high dosing - can be hepatotoxic
Delayed male puberty
Lack of testicular enlargement by 14 or incomplete genital growth with five years of initial puberty onset
Primary hypogonadism
Gonads fail, leading to a hypergonadotrpic state
Secondary hypogonadism cause
Often a constitutional delay of puberty can also be dues to illness or genetics
History factors that point to hypogonadism/delayed puberty
Failure to grow
Nutrition
Congenital abnormalities
Neurologic symptoms
Family history
Physical exam findings of hypogonadism
Arm span exceeding height by 5cm
Small testicular size (1-3 mL is prepubescent)
Low tanner stage
Finding that suggests CDGP as reason for puberty delay
Bone is younger than chronological age and growth pattern is normal
LH/FSH levels in primary and secondary hypogonadism
elevated in primary
decreased in secondary
Cryptorchidism
Testicles have not descended to the scrotum by 12 months of age - increases cancer risk
Management of constitutional delay of growth and puberty
Reassure patient, consider testosterone in patients whos self esteem is impacted
Testosterone replacement therapy for primary and secondary hypogonadism
Indefinite therapy for primary
Interrupt after 6 months for secondary to determine whether LH and FSH have been stimulated
Adding an aromatase inhibitor might allow for greater adult height
Effect of hypogonadism onset in the beginning of male fetal development
Ambiguous genitalia
Effect of hypogonadism in third trimester of fetal development
Cryptorchidism and micropenis
Clinical presentation of hypogonadism after puberty
Decreased energy
Loss of libido and morning erections
Loss of body hair
Increased fat mass
3 goals of a clinical evaluation of hypogonadism
Determine if it was before/after puberty
Determine state of genitalia
Determine if primary or secondary
Testosterone therapy indications
Lack of puberty onset by age 14
Primary testicular failure
Testosterone levels under 150 ng/mL
Andropause
Decrease in testosterone production between 4th and 6th decades of life
More common in those who are obese or have chronic illness
Testosterone therapy and screening for adult males recommendations
Routine screening not recommended
Replacement therapy indicated if 3 symptoms are present and testosterone is under 200ng/dL
5 symtpoms of low testosterone/hypogonadism
Poor morning erection, Depression, Fat gain, fatigue, low libido
Diurnal variation of testosterone
Highest at 8AM lowest at 8PM
Take a fasting specimen at 8-10 am
Next step after a low testosterone lab
Take a confirmatory sample
Lifespan testosterone levels
75-400 for first six months
Peaks in puberty at areound 1200
240-950 thereafter
Steady decline with age
When might you want to obtain a sex hormone binding globulin assay (2)
Suspected comorbid abnormality in testosterone binding
Indication to check LH/FSH levels
When further evaluation of testosterone levels is needed
Side effect of decreased sex hormone binding globulin
Increased estrogen
Indication for and meaning of inhibin B assay
Tests for damage to the sertoli cells
Decreased when there is damage
1 thing that can increase and 1 thing that can decrease Sex Hormone Binding Globulin
Age increases
Obestity decreases
3 hormones bound by sex hormone binding globulin
Testosterone
DHT
Estradiol
Semen analysis
Used for infertility, a normal sample excludes gonadal dysfunction
3 samples over 2-3 months
Use of a testicular biopsy
Distinguish between spermatogenic failure and ductal obstruction
True gynecomastia
Growth of glandular breast tissue (Not just fat) that is greater than 4cm in diameter and tender
3 normal places to see gynecomastia
New borns (from their mom)
Puberty
Aging with increased fat
4 things that can cause pathologic gynecomastia
hCG secreting tumors, Liver disease, Malnutrition, Hyperthyroidism
Historical findings for gynecomastia
Pain/Tenderness, Nipple sensitivity, Careful drug history
How will a breast malignancy feel
Unilateral, nontender, offset from the areola
Where will glandular tissue in gynecomastia be located
Symetric distribution below the areola
Causes of gynecomastia to assess for
Pubertal, Drug induced, Androgen deficiency, Tumor, Aromatization
Indications for testosterone replacement
Low testosterone and features of androgen deficiency - NOT helpful for infertility
Schedule of testosterone
Schedule III
Testosterone administration
IM followed by bimonthly regimen resulting in peaks and throughs
Injectable - long lasting - undecanoate
Gel - needs to be applied in an area that will not be touched (back?)
Testosterone therapy management
Monitor levels every 3-6 months
3 other things to check in testosterone management
Hematocrit
Bone mineral density
PSA, for men over 40
Testosterone contraindications (2)
CANCER - esp. prostate
CHF
Cholesterol
essential element of all animal cell membranes, precursor to steroid hormones and bile acids
Apolipoproteins
Protein required for the structure, function and metabolism of lipoproteins
KEY for lipids to move in and out of cells
Function of lipoproteins
Transport cholesterol, tryglycerides
Progression of lipoproteins
Become denser as deposit tryglycerides into the peripheral tissues
VLDL to IDL to LDL
Lipoprotein composition
Core of triglycerides and hydrophobic lipids
Shell of hydrophillic lipids and apolipoproteins
What changes as lipoproteins get denser
Less lipids, more apoprotein
Exogenous lipid pathway
Absorption of dietary lipids and formation of chylomicrons
Endogenous lipid pathway
Secretion of VLDL in the livier and its transformation to IDL and LDL
Transport of exogenous/dietary lipids
Broken down to chylomicrons in the GI tract
Absorbed and used via ApoCs
Broken down by LPL
Remnants travel to the liver to be taken up by LDL
Transport of hepatic or exogenous lipids
VLDL is derived in the liver and acquires ApoE and apoC from HDL
VLDLs are borken down by LPL for use
What happens to IDL that is formed from LDL after LPL activity
Taken up by the liver and systemically reduced to LDL. LDL May be removed from circulation for use in the bile
Synthesis of HDL
Reverse cholesterol transport, synthesized in the liver and intestines and recruits cholesterol
Role of HDL
Sweeps cholesterol out of circulation
Dyslipidemia
Disorder that results in increased plasma cholesterol and triglycerides along with low HDL - Often genetic
4 pathways to dyslipidemia
Excess hepatic secretion of VLDL
Impaired lipolysis of triglyceride rich proteins
Impaired hepatic uptake of ApoB contining lipoproteins
Inherited low levels of HDL-C
How does impaired lipolysis of triglyceride rich lipoproteins occur
Dysfunction of LPL
How does impaired hepatic uptake of apo-B containing lipoproteins usually occur
Down regulation of the hepatic LDL receptor
Pathophys of low HDL
Accelerated breakdown
Clinical presentation of dyslipidemia
Often asymptomatic
May present with eruptive xanthomas (pruritic patches on the skin, most commonly the buttocks)
Tendinous xanthomas
Lipid deposit nodules in the tendons of the hands, feet and heels
Seen with high LDL
Lipemia retinalis
Milky appearance of the veins on fundoscopic examination
Serum change of dyslipidemia
Serum may appear milky and opaque
Recommendation for lipid screenings
All adults beginning at age 20
Some suggest screening children at 9-11
6 ASCVD risk factors
Tobacco use
DM
HTN
Obesity (30+ BMI)
Family hx
Personal history of Atherosclerosis or Coronary artery disease
Non-fasting lipid labs we can take
Total cholesterol and HDL
Fasting labs for lipids and indication we need to take them
Non-fasting TC over 250 or HDL under 40
Full lipid panel - TC, LDL, HDL, TGs (9-12 hour fast)
HDL level that is cardioprotective
over 60 mg/dL
Screening schedule for lipids
Every 5 years for healthy adults
Every three years for those who may need therapy
65 is the suggested cutoff for screening
Four secondary causes of dyslipidemia to rule out
Hyperglycemia
Renal insufficiency
Hepatitis
Hypothyroidism
Four indications for statin therapy
Clinical ASCVD
DM
LDL over 190mg/dL
Primary prevention with ASCVD risk above 7.5%
Qualification for very high risk of ASVCVD
2 major events or 1 major event with 2+ high risk conditions
4 major ASCVD events
ACS within the past 12 months
History of MI
History of ischemic stroke
Symptomatic PAD
5 high risk conditions for ASCVD disease
Over 65
Smoking
Diabetes
LDL over 100 despite max statin use
CKD
Management of hyperlipidemia in those with ASCVD
High intensity statin if under 75 or very high risk
Moderate intensity statin if not very high risk or older than 75
2 high intensity statins
Atorvastatin
Rosuvastatin
Goal of hyperlipidemia management
50% reduction
V high risk - reduce to 55
Not V high risk - reduce to 70
Management of primary LDL over 190
High intensity statin reassessing every 4-12 weeks and then every 3-12 months
Goal of hyperlipidemia management with LDL over 190mg/dL
50% reduction or under 100mg/dL whichever is lower
Steps for 40-75 DM patient with LDL over 70-190
Calculate 10 year risk
Review diabetes high risk features
Management options and goals for Age 40-75 with DM and LDL 70-190
Those with >7.5%riskand 1 high risk factor need high intesnsity with 50% or <70mg/dL reduction
Otherwise - Moderate intensity with 30-49% reduction or under 100 mg/dL
Risk discussion for less than 5% risk of ASCVD
Emphasize lifestyle to reduce risk factors
Risk discussion for 5-7.5% risk of ASCVD
Consider moderate intensity statin therpay if risk enhancers are present
Risk discussion for 7.5-20% ASCVD risk
Moderate intensity statin with goal of 30-49% reduction
Risk discussion for 20+% ASCVD risk
Statin to reduce LDL to 50% or under 70mg/dL
3 risk enhancing factors for ASCVD
Metabolic syndrome
Family hx
CKD
CAC
Coronary artery calcium - low dose CT scan of the heart
Interpretation of CAC
Over 100 - add statin
1-99 - add statin if over 55
0 - Focus on lifestyle and reassess in 5-10 years
Assessment for patients initiated on statin therapy
Lipid panel every 4-12 weeks and then 3-12 months
Follow up for those with no therapy initiated
Recalculate ASCVD risk every 4-6 years
How long does it take for diet to impact hyperlipidemai
3-6 months
Mechanism of statins
HMG CoA reductase inhibitors - stimulate LDL catabolism
Reduction is dose dependent
Hepatic CYP450 metabolism
Side effects of statins
MYALGIA - less with pravastatin and fluvastatin
Hepatotoxicity
Hyperglycemia
Contraindicated in pregnancy
What to do when statin therapy is ineffective
Try adding another ststin or alternate regimen before trying a non-statin
Ezetimibe
Cholesterol absorption inhibitor - good choice because cheap - synergy with statin
2 PCSK-9 inhibitors
Alirocumab and Evolocumab
MOA and route of PCSK-9 inhibitors
Decrease LDL receptor degradation and increase LDL metabolism
SQ only
Bempedoic acid
ACL inhibitor that has some efficacy on treating hyperlipidemia - inhibits cholesterol synthesis - less effective with a statin more effective with absorption inhibitor
Side effects of bempedoic acid
Gout/Hyperuricemia - 70% urine excretion
Indication for bempedoic acid
Need LDL reduction while on max statin
Inclisiran
PCSK-9 small interfering agent day 1, 3 months, and then q 6 month dosing can cause arthralgia
better than other PCSK-9 inhibitors
3rd line treatment for hyperlipidemia
Bile acid sequestrants - Welchol
Safe in pregnancy
Impair absorption of other drugs taken 1 hr before or 4 hrs after
SEs of bile acid sequestrants
GI - nausea, bloating, etc.
Complication of hypertriglyceridemia
Pancreatitis
Casually related to CV disease
Indication for hypertriglyceridemia management of lifestyle modifications
Over 20 with TGs 175-499
Indication for statin therapy in hypertriglyceridemia
40-75, Over 7.5% ASCVD risk, TGs over 500
or TGs over 1,000 alone
Fibrates
Treat hypertriglyceridemia by stimulating LPL activity and apo-C III synthesis
Gemfibrozil, and fenofibrate
SEs of Fibrates
Dyspepsia, gallstones, myopathy
Caution in CKD can be hepatotoxic
Omega 3 FAs for hypertriglyceridemia
Need up to 4 grams/day
Can cause diarrhea or bleeding
Hicotinic acid (Niacin) for hypertriglyceridemia
Can cause flushing and increases LPL activity
MC inheritance pattern for metabolic mineral disorders
Autosomal dominant - often an enzyme deficiency
Sorbitol
Fructose alcohol
Glycogen storage disorder
Glycogen is stored excessively in the liver and the muscles and cannot be broken down leading to hypoglycemia during fasting
Clinical presentation of GSD
Lack of energy for exercise
Hypoglycemia with fasting
Delayed growth
3 things to evaluate for for GSD
Hypoglycemia
Elevated LFT
CPK for muscles
Genetic test - may be a replacement we can give
Fructosemia
Inability to break down fructose
Fructose 1,6 biphosphatase
Required for gluconeogenesis
Hypoglycemia during fasting when deficient
FDpase
Clinical presentation of 1,6 biphosphatase deficiency
Leads to hypoglycemia and acidosis
Avoid fructose and prolonged fasting
Aldolase B
In the initial breakdown of fructose
Aldolase B deficiency
Fructose 1 phosphate is deposited in the tissues and then causes organ damage
Jaundice, hepatomegaly, hypoglycemia
3 places fructose collects in an aldolase B deficiency
Intestines, Liver, Kidney
Essential fructosuria
No fructose kinase = no by products
Fructose in urine
Galactosemia
Inability to process galactose
3 enzymes that may be deficient in galactocemia
GALT, GALK, GALE
GALT deficiency
Decreased appetite, vomiting, jaundice - occurs right away because breast milk
Can develop cataracts due to galactitol deposition in the eye
GALK deficiency
Mainly cataracts with no other issues
GALE deficiency
Presentation depends on severity of deficiency
GALT deficiency screening and management
Often done on newborns
RBC galactose 1 phosphate
Avoid all dairy products
soy based baby formula
Mainainance for galactosemia
Take CBC and LFT yearly, Ophthalmology, Measure pubescent female hormones
Phenylketoneuria
Phenylalanine cannot be converted to tyrosine and it builds up in the brain causing myelin toxicity
Common ancestries of PKU pts
White or native american
Manifestation of PKU
Lighter hair and skin, loss of apatite, weakness, vomiting
4 things to avoid in PKU
Meat/Fish
Aspartame
Dairy
Nuts
2 drugs that treat PKU
Break down Phenylalanine
Sapropterin - Ped and adults
Pegvaliase - Adult only
Maple Syrup Urine disease
Can’t break down branch chain amino acids
Leucine, isoleucine and valine
Leucine buildup in the body
Neurologic issues
Isoleucine buildup in the body
Burnt sugary smell to urine
Clinical presentation of severe MSUD
Irritability, Rapid onset, Seizures and death
Clinical presentation of moderate MSUD
GI, muscle weakness, Eye symptoms, Hyperactivity
Management of MSUD
Specific branch-chain-controlled formula
Try a trial of thiamine for 4 weeks before formulation
Complication of MSUD
Metabolic decompensation - too much leucine
Hemodialysis, glucose, liver transplant last resort
Homocysteinuria
Interrupted breakdown of Methionine
Clinical presentation of homocystinuria
Dislocated optic lenses
retardation
Marfanoid
Pes excavatum
Genu valgum
Thromboembolic issues
Management of homocysteinuria
Give folate and B12 supplements
Limit protein intake
Lysosomal storage disorders
Abnormality in the biosynthesis or function of the lysosome
Tay-Sachs disease
Lysosomal storage disorder
Hexoaminidase buildup causes neurological damage
Infantile Tay Sachs
First 3-6 months
Abnormal startle reflex seen first - does not subside
Cheery red spot on fovea with gross motor delays
Lack of appropriate muscle tone
Common cause of death in infantile Tay Sachs
Pneumonia due to diaphragm weakness
Juvenile onset Tay Sachs
2-5 years
Respiratory infections and behavioral issues
Slow decline
Adult onset Tay Sachs
Report a hx of clumsiness in childhood
Weakness and dysarthria
Intelligence declines slowly
Treatment of Tay Sachs
Supportive care
Can diagnose via genetic testing
OT/PT
Gaucher (Go-Shay) Disease
Deficiency of Gcase leads to buildup of glucocerebrosides in Macrophages
Stuffed macrophages lead to tissue fibrosis
G1 Gaucher disease
Bone involvement - osteopenia and osteoporosis. No CNS involvement
G1&2
G2 most aggressive
G3 more insidious
Both cause neurological issues
Bone crisis
Gaucher cells cause clot and necrosis of bones - severe bone pain, sudden onset
Diagnostic for Gaucher disease
Low beta glucosidase enzyme activity - only screened in 4 states
Management of Gaucher disease
Recombinant enzyme replacement -won’t help neuro
Substrate reduction therapy - Eleglustat and miglustat
Fabry disease
Alpha galactosidase A (GLA) is deficient
X-linked recessive
Fat buildup on capillary wall prevents oxygen transfer
3Clinical presentation of Fabry disease
Small, non-blanchin lesions on umbilicus down
Decrease in sweating
Opaque cornea/lens from fatty deposits
Small vessel disease
Burning pain in extremities
Management for Fabry disease
Enzyme replacement with Fabrazyme
Can aso use migalastat
Consider statin therapy
Niemann-pick disease
Sphingomyelin cannot be broken down, fills macrophages causing cell death and tissue damage - FOAM cells
NP-A
Most aggressive niemann-pick - failure to thrive
Lung scarring
Hepatosplenomegaly
Die at 2
NP-B
Less serious
Lung issues, cirrhosis
Die in late adolescence
NP-C
CNS disease, Liver spleen and lung issues
Aspiration and muscle problems
Management of NP disease
NOT tested for in WV
PT/OT
Feeding tube
O2 therapy
Pompe disease
Deficiency of acid alpha glucosidase - can’t break glycogen into glucose - tissue destruction
Classic infantile Pompe disease
Few months after birth - progressive weakness - die before 1 year
Non-classic Pompe disease
Delayed motor skills - onset around 1 usually don’t make it past early childhood
Late onset Pompe disease
Less severe, often have respiratory failure as adults
Management of Pompe disease
Lunizyme - enzyme replacement therapy
Watch for sleep apnea, aspiration
3 things that can lead to hyperphosphatemia
Too much intake
Lack of excretion
Shift of phosphate from the inside to the outside of the cells (muscle or tumor breakdown)
Clinical presentation of hyperphosphatemia
Hypocalcemia or underlying condition
May need to diurese or dialyze
Phosphate binders also possible
Treat cause
Calcium acetate
Phosphate binder
for ESRD
Can cause GI side effects and cardiac arrhythmias
Compare risk/benefit for pregnancy
Lanthanum carbonate
Phosphate binder NOT preferred for pregnancy - binds in gut
Renagel
Phosphate that does not interfere with bicarb or calcium - may reduce vitamin uptake in pregnant patients - careful
3 things that can cause hypophosphatemia
Inadequate intake, increased excretion, shift of phosphate into cells
3 things that may caus inadequate intake of phosphate
Intestinal malabsorption
Antacids
Vitamin D deficiency
Cause of increase secretion of phosphate
Saline diuresis
Hyperparathyroidism
Fanconi
Cause of phosphate shifting into cells
Refeeding syndrome
DKA - when giving insulin
Increase in calcium due to bone disease
Level for severe hypophosphatemia
Under 2 mg/dL
Treatment for hypophosphatemia
Diet, supplements
Supplements can cause weakness, arrhythmia
Safe during pregnancy
Magnesium role
Energy transfer, storage, metabolism, PTH regulation
Source of magnesium
Green vegetables - low in alcohol abuse to TPN, Hungry bone syndrome, GI loss, NOT in a chamistry panel
Clinical presentation of hypomangacemia
Usually hypocalcemia symptoms and hypokalemia
Nystagmus horizontal and verticle
Management of hypomagnesemia
Dietary/supplement if mild
IV if severe
Pagets disease
Breakdown of bone followed by inappropriate reformation of bone
Clinical presentation of Pagets disease
Large vascular bones that get bent
Bone pain - deep and worse whn pt sleeps
Deformity
Compression of spinal nerves
Evaluation for Pagets disease
Elevated alkaline phosphatase
Non-uniform bones on X-ray (lytic lesion)
Can use a radionuclide scan to determine where the disease is active
Complications and management of Pagets
- neoplasms joint, and neuromuscular issues
Bisphosphonates to prevent osteoclastic activity
NSAIDS for joint pain
Calcium and Vitamin D
4 Bisphosphonates
Alendronate
Ibandronate
Risedronate
Zoledronic acid
Gene that is often suppressed in type 1 endocrine neoplasias
Menin encoded by the MEN1 gene
3 P’s of MEN-1
MC organs effected
Parathyroid
Pancreas
Posterior pituitary
Most common tumor types in MEN-2
Medullary thyroid
Parathyroid
Pheochromocytoma
3 most common tumor types in MEN-3
Medullary thyroid cancer, pheochromocytoma, Mucosal and GI ganglioneuromas
Presentation of MEN1 parathyroid tumor
Elevated PTH with asymptomatic mild hypercalcemia - use a nuclear scan to confirm
Treatment for MEN1 parathyroid tumor
Surgical PT gland removal
Cinacalcet
GEP-NET
Gastro-entero-pancreatic NeuroEndocrine Tumor
5 types of GEP-NETs
Gastrinoma
Insulinoma
Glucagonoma
VIPoma
Ppoma
Gastrinoma
A gastrin secreting tumor causing hypersecretion of gastric acid and peptic ulcers
Clinical presentation of a gastrinoma
GERD, Peptic ulcer disease, Hypercalcemia, Diarrhea
Gastric acid physiology 4 steps
Stimulation of gastrin by secretin
Gastrin secretion results in acid production
Gastric acid is released and travels to the duodenum where it…
Trigger secretin to be relased
Lab evaluation for gastrinoma
Fasting serum gastrin with 1000 pg/mL being diagnostic
if 150-1000 also do a secretin stimulation test
Management of gastrinoma
Convervative treatment:
PPIs - Omeprazole or Esomeprazole
H2 blockers - Cimetidine or famotidine
Surgery is controversial
Insulinoma
Beta cell tumor usually in the second to 4th decade of life
Clinical presentation of an insulinoma
Hypoglycemia with fasting - tremors, sweating, shaking, weakness
Lab evaluation for an insulinoma
72-hour inpatient fast while monitoring insulin levels
Should check for C-peptide to r/o factitious disorder
Management for insulinoma
Frequent Carb intake while waiting for surgery
Diazoxide (k+ channels) and Octreotide (somatostatin analogue) can help
Surgery is 1st line
Clinical presentation of glucagonoma
Hyperglycemia
Weight loss
Necrolytic migratory erythema around orifices
Lab evaluation for glucagonoma
Elevated blood glucose and elevated fasting glucose
Control BS, Octreotide, Excise IF one lesion can be identified
VIPoma
Pancreatic tumor that secretes vasoactive intestinal polypeptide
Clinical presentation of VIPoma
Severe tea colored diarrhea
Flushing
Inhibition of gastric acid secretion
Bone resorption
Hyperglycemia
Lab evaluation for VIPoma
Serum VIP over 75 pg/mL confirmed by repeat testing
Management of VIPoma
Correct fluid electrolyte and vitamin imbalances - B12 can’t be oral
Octreotide to inhibit VIP
Surgical excision if no mets
2 types of nonfunctioning pancreatic tumors
Ppomas (polypeptide secreting)
Non-functioning NETs
Progression of nonfunctional pancreatic tumors
May metastasize to the liver as they are not symptomatic
Management of non-functioning pancreatic tumors
Surgery is controversial - evaluate for metastasis - don’t operate w/ mets!!
Iatrogenic diabetes, steatorrhea, dumping syndrome may result
MC secretions of pituitary adenomas
60% prolactin
25% GH
5% ACTH
10-20% Non-secretory
Lab evaluation and management of pituitary adenoma
Hypothalamic-pituitary testing
Transsphenoidal surgery for removal
Cabergoline for prolactinoma
Octreotide for GH secreting
Pasireotide for ACTH secreting
Adrenal adenoma management
Excise if over 4cm
Carcinoid tumor
Slow growing tumor of the bronchi or GI tract - asymptomatic until late in disease - excise
Meningioma
Tumor of the meninges that should be referred to a neurosurgeon
3 other possible MEN-1 tumors
Lipoma, Angiofibroma of face, Thyroid tumor
When to screen for MEN-1
Two or more associated tumors
First degree relatives have it even if asymptomatic
Wermer syndrome
MEN-1 from menin gene issue
MEN-2
Mutation in RET-proto oncogenes causing thyroid, parathyroid, and adrenal cancers
3 subtypes of MEN-2
MEN-2A
MEN-2B (MEN 3)
Familial medullary thyroid cancer
Clinical presentation of medullary thyroid cancer
Increased secretion of calcitonin may include nodules and hoarseness
Diagnostics for medullary thyroid cancer
Serum calcitonin and FNA biopsy
Treatment for medullary thyroid cancer
Total thyroidectomy
Treatment for pheochromocytoma
Surgical resection w/ alpha blockade while waiting
Additional symptoms of MEN-2B
High arched palate, Pectus excavatum, High arched feet, scoliosis
What should be done before removing any tumors
Remove a pheochromocytoma FIRST
Neuroma
Tumor of the tip of the nerves - seen in MEN2B along with lip hypertrophy
Screening guidlines for MEN2/3
All patients with Medullary thyroid cancer
MTC and hx of family tumors
MTC and pheochromocytoma
Unilateral pheo and increased calcitonin
MEN-4
Rare and autosomal dominant
Tumors are similar to MEN1
Autoimmune Polyendocrine syndrome
Rare immune endocrinopathies characterized by combined gland insufficiencies
Clinical presentation of APS 1 -3 key symptoms
Chronic mucocutaneous candadiasis
Acquired hypoparathyroidism
Adrenal failure
Pretty much everything gets attacked
Management of APS type 1
Always treat addisions FIRST can use ketoconazole for candidiasis
APS 2
HLA gene mutation
APS 1
AIRE gene mutation
4 criteria for APS-II
Primary adrenal failure, Autoimmune thyroid disease, T1DM, Primary hypogonadism
Diagnostics and monitoring for APS-II
No specific genetic test, monitor every 1-3 years
Condition to treat before treating other endocrine conditions
Addison’s disease
Storage of glycogen
In the liver and muscles
Metabolism of glycerol and fatty acids
Glycerol becomes glucose
Fatty acids become ketones cannot become glucose
Cell that secretes insulin
Beta cell
Part of insulin that is cleaved off duing production
C-peptide
GLUT-2 receptors
Transport glucose into body cells - insulin independant
GLUT-4 receptors
Insulin dependent transport of glucose into adipose and muscle tissue
How does glucose signal the pancreas to secrete insulin
It enters the beta cell, goes through glycolysis to form ATP which inhibits at K+ channel causing depolarization and insulin release
How does insulin work in the body
Increases transport of macronutrients into the body cells and their synthesis except for gluconeogenesis
Cells that secrete glucagon
Alpha cells
Action of glucagon
Increased breakdown and gluconeogenesis
Action of amylin
Secreted with insulin and C-peptide
Works with insulin and increases satiety
Somatostatin
Secreted by delta cells
Suppresses insulin, glucagon and other hormones
Incretins
Gut derived hormones that promote insulin release after an oral nutrient load leading to slowed gastric emptying and increased satiety
3 counter-regulatory hormones to insulin
Epinephrine
Growth Hormone
Glucocorticoids
Two types of Type I DM
IA - Autoimmune (most of cases)
IB - Idiopathic
Pathogenesis of T1DM
Genetic with an immune trigger
Use of immunosupressabts in T1DM
No beneift noted
T1DM immune markers
Anti-GAD65 is the main one - markers decrease as beta cells are destroyed
Pathogenesis of T2DM
Resisitance of the tissues to insulin, leading to inadequate insulin secretion
Environmental with obesity being the number 1 factor
What happens in the liver during T2DM
The liver continues to make glucose leading to increased hyperglycemia
T2DM Ominous Octet
Decreased insulin secretion
Increased hepatic glucose production
Decreased peripheral glucose uptake
Increased lipolysis
Decreased incretin effect
Increased glucagon secretion
Decreased neurotransmitter function
Increased renal glucose reabsorption
Fasting and postprandial glucose levels that makr diabetes
126 fasting
200 postprandial
A1c for diabetes
6.5+
A1c for prediabetes
5.6-6.4
Criteria for metabolic syndrome
3+ of five criteria
Fasting TG over 150
HDL under 40
BP over 130/85
Fasting Glucose over 100
Waist circumference over 40(M) 35(F)
If they are on meds for any of these conditions that counts
2 ethnic groups at the highest risk for Metabolic syndrome
Mexican Americans, blacks
Insulin effect on sdium, blood vessels and lipolysis
Retains sodium, dilates blood vessels, leads to FFAs in blood stream
In insulin resistance it still retains sodium but DOES NOT dilate blood vessels
Adiponectin
Anti-inflammatory cytokine produced by fat cells that is reduced in patients with metabolic syndrome
3 conditions commonly associated with metabolic syndrome
Hyperuricemia, PCOS, Obstructive sleep apnea
Suggested calorie restriction for MetS
about 500 per day
Physical activity suggested for MetS
at least 30 minutes per day - more for weight loss
3 poly’s of a general diabetes presentation
Polyuria
Polydipsia
Polyphagia
How does T1DM cause blurry vision
Hyperosmolar tears blur the vision
Dual peak of T1DM incidence
4-7 or 10-14
4 potential exam findings for T2DM
Poorly healing footh ulcer, Balanoposthitis, Rash in intertriginous fold, Acanthosis nigricans
Clinical presentation of hypoglycemia
Trembling, Diaphoresis, Feeling faint, Tachycardia, confusion
Who should be screened for diabetes
All adults at 45
Any patient who is obese or has 1+ DM risk factors
1st prenatal visit
HIV+
Prediabetic fasting and postprandial glucose
Fasting - 100-125
Postprandial - 140-199
How many tests do we need to confirm a diabetic diagnosis
Abnormal blood sugar must be repeated once
Best location for glucometry
Finger tip - other areas can be behind in the reading
What does A1c indicate
Glycemic state over the past 8-12 weeks - more heavily weighted to the last 4 weeks
False low A1c readings
High levels of HbF
Shortened erythrocyte survival (hemolytic anemia)
IV drugs or iron
False elevations in A1C
Splenectomy leading to decreased turnover
Stress over a long time
3 interpretations for a low A1c
Hemolytic anemia, chronic blood loss, chronic renal failure
Special education for glucose tolerance testing
Eat at least 150g of carbs daily three days before test
Avoid physical activity and smoking until test is complete
Use of C-peptide testing
Determines beta cell function, causes of hypoglycemia, evaluation of insulinomas
Normal C-peptide:Insulin ratio
5-10
Indication for ketone testing
Evaluation for ketosis - can test serum or urine
3 ketone bodies and which is predominant in DKA
Acetone, Acetoacetate, beta-hydroxybutyrate (BHB is most common in DKA)
Ketone level that is concerning
Greater than 3
Which ketone test is more reliable
Serum ketones because it picks up beta-hydroxybuterate
3 general goals of DM treatment
Glycemic control
Reduction or elimination of complications
Maintain quality of life
Fasting BS
Postrprandial BS
A1c
Desired for patients who are diabetic for glycemic control to be acheived
A1c - Under 7%
Fasting BS - 80-130
Postprandial BS - Under 180
Targets for pediatric patients with DM
A1c under 7.5
Fasting BS 90-130
Postprandial BS 90-150
Hypoglycemia management in conscious patient
Give 15-20g glucose orally
Eat a snack or meal when glucose returns to normal
Hypoglycemia management in an unconscious patient
IV glucose with nasal glucagon
DM nutrition guidelines
Low carb, T1 shoudl eat consistently, Dietary fiber prevents glucose absorption
Encourage weight loss in type 2
DM exercise recommendations
150min/week min
Resistance training
no more than 2 days w/o exercise
BMI at which to consider pharmacotherapy
27
BMI at which to consider bariatric surgery
30 (27.5 for asian americans)
2 best antihypertensives for DM
ACE or ARB ~Pril or ~Sartan
Management of hyperlipidemia in DM
Yearly lipid profile recommended
Management of ASCVD in DM
Consider aspirin if risk greater than 5%
Management of diabetic nephropathy
Yearly check of urine albumin and eGFR for diabetics who have been for over 5 years
Management of DM retinopathy and feet
Dilated eye exam at time of diagnosis for T2
After 5 years for T1
Preform yearly
Same for feet
Screening for diabetic neuropathy
Monofilament and one other test (ie. vibration)
Educate patients on foot care
5 Exams DM patients need once a year at least
Eye exam
Foot exam
BP (every visit)
Psych eval
Check on ASA therapy
4 labs DM patients should get taken yearly
eGFR
Urine albumin
Lipid profile
A1c (twice per year)
Where to put moisturizer on diabetic feet
Everywhere but NOT between toes
Side effects of insulin injection
Hypoglycemia
Lipohypertrophy or lipoatrophy at injection site
Alcohol effect on the insulin dependant
Causes hypoglycemia (liver stops doing gluconeogenesis)
Common dosing for insulins
U100 (100units/mL)
Basal insulin
50% of insulin given, long acting background
Bolus insulin
Other 50% covers meals
5 bolus insulins
Lispro
Aspart
Glulisine
Technosphere (IN)
Human REGULAR
5 Basal insulins
Human NPH
Detemir
Glargine (U300 is ultra long)
Tresiba (ultra long)
Pro/Con of inhaled insulin
Rapid acting
Not for smokers and can cause cough and lung cancer
Pro/Con of premixed insulins
Fewer injections but less easy to control dose
Insulin needle guage
31 or 33
4 insulin injection sites
Upper outer arms
Abdomen
Buttocks
Upper outer thighs
Proper injection regimen for insulin
Choose 1 site but rotate spots within that site
Guidelines for Males and Females for DM carb counting
M - 60g per meal 30g per snack
F - 45g per meal 15g per snack
Dawn phenomenon
Hyperglycemia that occurs in the morning due to the body naturally countering the effects of insulin
Somogyi effect
Hyperglycemia that occurs because of excessive nocturnal insulin - high BS is a rebound reaction
2 ways to differentiate between Dawn and Somogyi
Check BS at 3 am Low=Somyogi, Med/High=Dawn
Decrease bedtime insulin improves with somyogi, gets worse with Dawn
Slow absorption and fast absorption insulin injection sites
Abdomen and buttocks are fast
Legs and arms are slow
Physiologic insulin regimen
4 injections per day 3 rapid and 1 long basal
half basal, half for boluses
or 1 unite per 15 g of carbs
ACHS
How to use Blood sugar readings in adjusting insulin dose
Adjust insulin dose taken at the meal BEFORE the one for which you are checking glucose
Dose adjustments for high or low sugars
Under 80 (or 125 before bed) subtract 2 units
Over 130 (or 150 before bed) add 2 units
Under 70 eat something sugary
Best insulins for basal doses
Long acting (ie. lantus) better than NHP
Toujeo and Tresiba have less hyperglycemia
BID premixed dosing insulin regimen
2 injections per day
2-3 checks per day
Starting dose for premixed insulin
10% of the patients weight in units
Sliding scale insulin
Usually used in inpatient settings
uses a reactive approach to control and can result in wide swings
Metformin
Biguanide - FIRST LINE
Inhibits hepatic gluconeogenesis
Decreases glucose absorption
Slightly improves insulin sensitivity
Pro/Con of metformin
Cheap, weight loss, good lipid profile
GI side effects, metallic taste, B12 deficiency, can cause lactic acidosis
A1c reduction with Metformin
1-2%
TZDs
Rosiglitazone and Pioglitazone
Unlock muscle and fat cells and improve insulin sensitivity
A1c increase from TZDs
.5-1.4%
TZD MOA
Bind to PPAR gamma cause an increase in adipogenesis
TZD pro/con
improves fasting and postprandial glucose like metformin
Improves TG requirements and lowers insulin needs
Weight gain edema, BBW for CHF
3 Sulfonylureas and 2 Meglitinides
Glimepiride
Glipizide
Glyburide
Lower A1c by 1-2%
Repaglinide
Nateglinide
Lower A1C by .5-1%
Pro/Con of sulfonylureas/meglitinides
Cheap, Short onset, improves XFBG and PPBG
Hypoglycemia, Weight gain, liver/renal disease, TID
Alpha glucosidase inhibitors
Block breakdown of starches in the intestine and delay carb absorption
Acarbose and Miglitol
Reduce A1c by .5-.8
Pro/Con of alpha glucosidase inhibitors
Improve PPBG without hypoglycemia
Flatulence, TID, May increase hypoglycemia in combo with SFUs or insulin
SGLT2 inhibitors
Halt renal glucose absorption in the PCT
(sugar flows in the toilet instead)
Canagliflozin
Dapagliflozin
Empagliflozin
Ertugliflozin
Pro/Con of SGLT2 inhibitors
Weight loss, CKD improvement, Lower BP
UTIs, increases LDL, May mask DKA
GLP-1 receptor agonists
Mimic GLP-1 increase insulin, decrease glucagon, decrease gastric emptying end in TIDE - Incretin related
Oral GLP agonist
Rybelsus/Semaglutide
Pro/Con to GLP-1 receptor agonists
Improves FBG and PPBG without hypoglycemia, weight loss
Mostly SC, BBW thyroid cancer, GI effects
DPP-4 inhibitors
Extend effects of Incretin by inhibiting its degradation
END in Liptin
Pro/Con of DDP-4 inhibitors
Improves FBG and PPBG
Pancreatitis, GI but less than GLP-1 aggies
May cause increased risk of heart failure
Amylin analogs
Pramlitide
decrease glucagon and gastric emptying while increasing satiety A1c increase of .25-.5%
Pro/Con of amylin analogues
Glucose and weight improvement
Can help with Type 1 OR 2 diabetes
Must be SC, can cause hypoglycemia - BBW
Covesevelam
Bile acid qequestrant lowers A1c by .3-.5% and reduces LDL
GI effects of Constipation and Dysipepsia
Bromocriptine
Dopamine receptor agonist that lowers A1c by .1%-.5%, N/V, dizziness, HA
