Week 3 Endocrine Flashcards
T/F: Gout is more common in men than women?
True
Prevalence increases with age, >65
Gout considered a musculoskeletal disorder or metabolic disorder?
Both
Metabolic disorder b/c of purine metabolism
Musculoskeletal disorder b/c monosodium urate crystal deposition in and around joints.
What are some risk factors of Gout?
- Positive Family History
- Older Age
- Male
- Overweight
- Other chronic conditions (CKD, Hypothyroidism, Infections)
- Post-surgery
- Some Medications (E.g. Diuretics, low dose ASA)
- Alcohol
Etiology of Gout: Primary vs Secondary
Primary - High levels of uric acid result from either increased production or decreased excretion rates of uric acid
Secondary - Hyperuricemia results from primary disease processes such as HTN, HF, kidney disorders.
What medications can induce hyperuricaemia or gout?
Diurectics, ASA, ETOH, nicotinic acid, ethambul (anti-TB), pyrazinamide (anti-TB).
Drugs raise serum uric acid level by increasing uric acid reabsorption and/or decreasing uric acid secretion in gout.
Adequate hydration and routine uric acid level monitoring should be encouraged for drugs known to induce hyperuricaemia.
Drugs are FACT
- Furosemide
- Aspirin, alcohol
- Cyclosporin
- Diurectics (loop diuretics, thiazide diuretics and thiazide-like diuretics)
Pathophysiology of Gout
Uric acid can be obtained from the diet or made endogenously by xanthine oxidase, which converts xanthine to uric acid
An excess of uric acid results in hyperuricemia
Uric acid can deposit in the skin/subcutaneous tissues (tophi), synovium (microtophi), and kidney, where they can crystalize to form monosodium urate crystals that lead to gout
Uric acid crystals trigger an inflammatory response
Stages of Gout - initial phase:
Acute gouty arthritis
-sudden onset; maximal severity of the flare reached within 12-24 hours
-attack will subside spontaneously within 5-10 d; may recur
-red, hot, painful to touch, swollen
Stages of Gout - in between phase:
Intercritical gout (period without flares)
*pain free
Stages of Gout - chronic phase:
Chronic/tophaceous gout
*progression of gout has been inadequately treated resulting in urate crystal deposits (tophi) in the joints that can cause deformity and disability of the joint
Onset of gout flares at night or during the daytime?
night time
What joint is normally affected?
Base of great toe metatarsophalangeal joint or knee
*initial normally affects single joint (80%)
*polyarticular flares (20%) of initial flares with increased reoccurrence with untreated gout
What is the difference btwn gout flare and cellulitis?
limited mobility with gout
mobility is preserved with cellulitis unless infection over a joint
What connective tissues can urate crystals (tophi) be deposited?
cartilage, tendons, bursae, soft tissues, and synovial membranes
What are the common sites of urate deposits?
first MTP, ear helix, olecranon bursae, tendon insertions (common in Achilles tendon)
What are some medical complications that can arise from or be worsened by obesity?
DMT2, gallbladder disease, NAFLD, gout
Excess and ectopic body fat are important sources of adipocytokines and inflammatory mediators that can alter glucose and fat metabolism, leading to increased cardiometabolic and cancer risks, and thereby reducing disease-free duration and life expectancy by ____to _____ years.
6 to 14 years.
It is estimated that 20% of all cancers can be attributed to obesity, independent of diet.
Obesity increases the risk of the following cancers:
Colon (both sexes)
Kidney (both sexes)
Esophagus (both sexes)
Endometrium (women)
Postmenopausal breast (women)
People living with obesity experience something that contributes to increased morbidity and mortality, and it is independent of weight or BMI. What is it?
Pervasive weight bias and stigma.
What are the 5 A’s for obesity management in adults?
Ask - would it be alright if we discussed your weight?
Assess - Value-based goal that matters to the patient, obesity classification, adiposity-related complications, disease severity
Advise - discuss obesity risks, health benefits of obesity management
Agree - on realistic expectations, sustainable behavioural goals and health outcomes. Agree on a personalized action plan.
Assist - identify drivers and barriers, provide education and resources.
There are 4 medications approved for use in obesity management in Canada (as per Cdn guideline). What are they?
There are four medications indicated for long-term obesity management in Canada as adjuncts to health-behaviour changes:
liraglutide (Saxenda®),
naltrexone/bupropion (Contrave®) in a combination tablet,
orlistat (Xenical®) and
semaglutide (Wegovy®).
All four medications are effective in producing clinically significant weight loss and health benefits greater than placebo over a duration of at least one year.
Obesity medications are intended as part of a long-term treatment strategy. Clinical trials of pharmacotherapy for obesity management consistently demonstrate regain of weight when treatment is stopped.
True or false?
True!
According to the Cdn guideline, when should you consider treating obesity with pharm?
Pharmacotherapy for obesity management can be used for individuals with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 with adiposity-related complications, in conjunction with medical nutrition therapy, physical activity and/or psychological interventions.
What is the recommended management approach if your patient has severe mental illness and is gaining significant weight assoc. with their anti-psychotic medications?
Metformin + psychological tx such as CBT
T/F: Vitamin C is recommended for prevention of acute gout attacks?
False. Not effective in lowering serum uric acid levels.
Is a low calorie diet just as acceptable and beneficial if not more than a low purine diet to reduce the risk or frequency of gout flares?
Yes. Recommend one less portion of meat or seafood per day.
Encourage low-fat or non-fat dairy products & vegetables
it can be impossible for patients to limit their purine intake enough to significantly alter their risk of a gout flare, and dietary restrictions could result in other nutritional deficiencies.
An excess of uric acid is called hyperuricemia. How does uric acid even develop?
Uric acid can be obtained from the diet (break down purine) or made endogenously by xanthine oxidase, which converts xanthine to uric acid
Purine is naturally occurring in our body, but is also found in certain foods
- A purine-rich diet can ↑ serum uric acid by 1 to 2 mg/dL (~60 to 120umol/L)
What foods are high in Purine?
Food is SALT (S)
Seafood
(Avoid sardines, shellfish)
Alcohol
(Avoid alcohol overuse: >2 servings/day in males & > 1 serving/day in females; limit beer)
Liver and Kidney
(Avoid high-purine organ meats; limit beef, lamb, pork,)
Turkey
Syrups/sugars, sweetened sodas
(Avoid high fructose corn syrup sweetened sodas, beverages, or foods; Limit naturally sweet fruit juices, table sugar, sweetened beverages & desserts, table salt (including in sauces & gravies)
What are the differentials of Gout?
Infectious arthritis.
Hyperparathyroidism.
Pseudo gout (commonly occurs in the knee wrist or other joint, bursitis)
Cellulitis.
Bursitis
When is it appropriate to draw a serum urate blood test when assessing for gout?
Blood test: urate levels may or may not be elevated in a flare – most accurate time for assessment of serum urate is at least 2 weeks after a flare
What is the mechanism of an antihyperuricemic drug?
decrease uric acid production by inhibiting xanthine oxidase. Start low and titrate up.
Use when maintaining or preventing further flare ups.
When would you consider starting an antihyperuricemic drug?
*>2 attacks/year, bone erosions/arthritis
*chemotherapy
*sUA >800 umol/L
* advanced dx tophus/tophi or radiographic damage or urolithiasis;
*CKD >Stage 2
What is first line treatment when maintaining gout flares?
Allopurinol
What is treatment for acute gout flares?
Rapid treatment initiative - within 24hrs
Colchicine, NSAIDs, or corticosteroids all 1st-line & effective;
consider CI/DI/AE. Start at high dose, then taper.
From Gayle’s pres in 543:
An example for a patient with 4 gout attacks per year, decision made to start prophylaxis:
Colchicine 1.2 mg x 1 stat, then 0.6 mg x 1 hr on day #1
– Then Colchicine 0.6 mg daily for 3 months
– Start allopurinol 100mg daily 10 days after acute gout flare
– Titrate up by 100mg every 2 weeks, up to 300mg daily and R/A
– Allopurinol 300mg daily is a common dose
Or
Ibuprofen 600mg TID with Pantoprazole 40mg daily for 7 to 14 days
– Then Ibuprofen 400mg BID or TID for 3 months, preferably with PPI for GI protection.
– Start allopurinol 100mg daily 10 days after acute gout flare
– Titrate up by 100mg every 2 weeks, up to 300mg daily and R/A
– Allopurinol 300mg daily is a common dose
ASA and thiazide are risk factors? Do you still prescribe if someone is high risk CV disease?
Yes
Are glucocorticoids useful in treatment of gout?
Yes. Decreases pain and inflammatory response; effective for gout equal to NSAIDs. Useful if CI/AE to NSAIDs or colchicine e.g. renal, transplant, warfarin pts, etc.
May add acetaminophen for pain
When treating an older adult, what is the recommended starting dose as well as titration dose when prescribing allpurinol?
If CKD , hepatic impairment , or elderly,
initiate at 50mg po daily cc & increase by 50mg q2-4wks.
If an older adult is complaining of weakness and functional decline with history of gout, what investigations should be completed? (if they are on colchicine)
Colchicine – myopathy and peripheral neuropathy can be subtle in older adults, although brief courses (eg, less than a week) for gout flares should not be associated with these complications.
- In case of longer courses or frequent use, complaints of weakness and functional decline while taking colchicine should prompt a careful neurologic examination, laboratory evaluation including a serum creatine kinase, and empirical drug discontinuation
What are the contraindications of NSAIDS in older adults?
Heart failure, kidney dysfunction, or gastrointestinal disease.
In the absence of such contraindications, indomethacin in older adults because of the greater risk of adverse effects with this medication compared with other NSAIDs.
Can we prescribe glucocorticoids to older adults?
Brief courses of oral glucocorticoids are generally tolerated in patients in whom NSAIDs or colchicine may pose an increased risk.
What is another name for pseudogout?
calcium pyrophosphate dihydrate (CPPD) Disease
What is CPPD disease?
An acute inflammatory condition primarily affecting the larger joints in which crystal deposits occur in the connective tissues
What connective tissue CPPD primarily attack?
synovial membrane/joint
crystal formation in the cartilage that shed into joint
Is CPPD painful?
Not always - can clinically present like urate gout but pt can be asymptomatic to painful attacks. Majority of individuals are asymptomatic.
Acute attacks of CPPD can happen more often in women than men?
Men more often have acute attacks
Women with OA and CPPD may have a higher incidence of occurrence
“OA with CPPD is the most prevalent form of symptomatic CPPD disease. Approximately 50% of patients with symptomatic CPPD disease show progressive joint degeneration of multiple joints. This pattern of disease is referred to as “pseudo-OA” because of its resemblance to OA occurring in the absence of CPPD. Approximately 50% of such patients, episodes of acute inflammation typical of pseudogout punctuate the course, but for the rest joint degeneration proceeds by a process more typical of classical OA.”
Is gout associated with CPPD disease?
Can be…approximately 5% of patients have gout with CPPD disease.
What are the consequences of CPPD deposits?
*Acute inflammatory arthritis
*Inflammatory and degenerative chronic arthropathies
*Radiographic cartilage calcification and constitute the spectrum of CPPD disease (Rosenthal, 2018a).
Radiographic calcification is commonly seen in patients with CPPD, but is not specific, and therefore not pathognomonic.
Risk Factors of CPPD?
- Idiopathic
- Older age
- Joint trauma
- Hospitalization/illness
- Familial chondrocalcinosis
- Endocrine/metabolic disorders: gout (5%), hyperparathyroidism, hemochromatosis, hypophosphatasia, hypothyroidism, hypomagnesaemia, Gitleman’s syndrome, hemosiderosis
Age group who primarily is affected with CPPD?
50% of cases in those older than 84; 36% in ages 75-84; 15% in age 65-74
Which joint is primarily affected with CPPD?
Joints affected: knee approximately 50% of the time. Others: wrists, shoulders, ankles, feet and elbows.
Why is CPPD difficult to diagnose?
Can mimic other types of arthritis including gout, rheumatoid arthritis, osteoarthritis, and neuropathic joint disease.
What is asymptomatic CPPD disease?
Most joints in which CPP crystal deposition is apparent on x-ray are asymptomatic. This is true even among patients in whom acute or chronic clinical manifestations of CPPD disease in 1 or more other joints has occurred. However, with targeted questioning, these patients with apparent asymptomatic CPPD may be found to have manifestations of an arthritic disorder.
What are the precipitating events for acute CPPD disease?
- Trauma, surgery, or severe medical illness often provoke acute attacks.
- In particular, flares of acute CPP crystal arthritis after parathyroidectomy have been observed, perhaps due to associated precipitous changes in calcium and magnesium levels.
Three types of CPPD disease that Don wants us to understand.
Asymptomatic CPPD disease; Acute CPPD arthritis; Chronic CPP crystal arthritis
S&S of Acute CPPD arthritis?
Characterized by self-limited acute, or subacute, attacks of arthritis involving 1 or several extremity joints.
S&S of severe acute inflammation with intense pain, redness, warmth, swelling, and joint disability.
There can also be inflammation of several adjacent joints (cluster attacks) or petite attacks (minimally painful episodes of joint warmth and swelling) (Rosenthal et al., 2018b).
How to decipher btwn CPPD and urate gout?
In order to help differentiate CPPD from urate gout, think location and duration of symptoms.
LOCATION
- The knee is affected in >50% of all acute attacks of CPPD, while the 1st MTPJ is most frequently affected in urate gout.
- Other joints typically affected in acute CPP crystal arthritis include wrists, shoulders, ankles, feet, and elbows.
- An upper extremity site of inflammation (wrist, elbow, shoulder) for a first attack should raise suspicion for acute CPPD arthritis
DURATION
Initial episodes of acute CPPD may persist longer before remitting than do episodes of urate gout, which typically last 1-2 weeks.
CPPD rarely have visible masses of crystals in synovium and adjacent joint structures, resembling gouty tophi.
- These masses can cause local pain/compressive symptoms.
Associated symptoms r/t Acute CPPD arthritis?
- Low grade fevers and elevated ESR
What is chronic CPP crystal arthritis?
The term pseudo-rheumatoid arthritis has been used to describe a non-erosive, inflammatory arthritis in which CPP crystals are demonstrated in joint fluid.
Chronic CPP occurs in ≤5% of patients with symptomatic CPPD, and most of those are older adults
S&S of chronic CPP crystal arthritis?
*Resembles RA, with significant morning stiffness, fatigue, synovial thickening, localized edema, and restricted joint motion, due either to active inflammation or to flexion contractures.
*Systemic features of leukocytosis, fever, mental confusion, mimicking sepsis is also seen.
Primary locations of chronic CPP crystal arthritis?
*Multiple joints, frequently in peripheral joints of the upper and lower extremities, (wrists and MCPJs), as well as the knees and elbows.
*Usually symmetric.
Duration of chronic CPP crystal arthritis?
*Articular inflammation may last several months.
*Inflammation of the various joints involved tends to wax and wane independently of one another.
**This is in contrast to RA, where synchronous flare and remission are typical.
*Episodes are self-limited, lasting days to weeks.
What is the most prevalent form of CPPD Disease?
OA with CPPD
Progressive joint degeneration of multiple joints - ‘pseudo-OA’
Location of OA with CPPD?
*Knees are most often affected, followed by the wrists, MCPJs, hips, shoulders, elbows, and spine.
*Pattern is frequently symmetric, but unilateral or more severe degenerative change unilaterally, is also found.
*Typically involves same joints as in OA (interphalangeal joints of the hands, the 1st CMCJ, the knees, or the 1st MTPJ.)
**The first carpometacarpal joint (CMCJ) is located at the base of the thumb, where the metacarpal bone of the thumb articulates with the trapezium bone of the wrist.
*An etiologic or accelerating role for CPP crystal deposition in joint degeneration seems likely when radiographic calcification is present early in the course of degeneration, particularly if the degenerative changes also involve joints atypical for OA (wrists, MCP joints, elbows, and shoulders) in the absence of a preceding history of joint trauma or stress.
S&S of OA with CPPD?
- Clinical examination of individual joints does not typically differ from those observed in OA:
- asymmetric bony enlargement
- tenderness
- effusions
- crepitus
- restricted joint motion.
- Patients also develop contractures of involved joints and valgus deformities of the knees.
Diagnosis criteria of CPPD?
Suspected in the patient:
- most often > 65
- with acute or subacute attacks of arthritis (particularly of the knee),
- arthritis similar in character to RA or OA,
- apparent CPPD crystal deposition on radiographs
- in patients with other selected but less common presentations (Rosenthal et al., 2018b).
Diagnosis is largely based upon the demonstration of CPP crystals in tissue or synovial fluid and/or upon radiographic evidence of the disease.
Generally, differences between the patterns of joint involvement in urate gout and acute CPP crystal arthritis are insufficient to permit definite diagnosis without demonstration of the specific crystal in the inflammatory joint effusion.
Differentials of CPPD?
Gout
Septic arthritis
OA
RA
What imaging is recommended to help diagnose CPPD?
Radiography, US, or CT - MRI not sensitive enough
Imaging reveals:
*evidence of cartilage calcification (chondrocalcinosis)
*degenerative changes in the joint
After determining the type of crystal in tissue fluid and /or radiographic evidence, and there is a positive diagnosis of calcium CPPD disease, what other conditions should you investigate then?
- hemochromatosis
- hyperparathyroidism,
- hypomagnesemia,
- hypophosphatasia,
- familial hypocalciuric hypercalcemia (FHH)
When investigating associated conditions what BW should you order?
- Calcium,
- Phosphorous
- Mg
- parathyroid hormone (PTH)
- ALk. Phos.
- Ferritin
- iron and transferrin.
