SIADH

Pt with h/o cerebral tumor presents with new onset hyponatremia s/p surgery. Symptoms of fever, headache, neck stiffness, SOB additionally concerning for pneumonia, meningitis. Medications include amiodarone, carbamazepine, chlorpromazine, SSRI. Denies use of diuretics, Ecstasy. Does not eat low salt diet. Fever, MMM, nuchal rigidity, pulmonary crackles, euvolemia on exam.

• Labs

  • Serum mOsm: [(Na x 2) + (glucose / 18) + (BUN / 2.8)] < 280

  • Urine Na > 40 mEq/L and urine osmolality > 100 mOsm/kg

  • Serum BUN:Cr ratio, TSH within normal limits

  • Urine drug screen negative

• Trial of 1L NS

  • SIADH indicated by decreased sodium levels s/p bolus

  • If urine Na > 40 mEq/L or urine Osm < 100 mOsm/kg s/p bolus, reconsider hypovolemic hyponatremia

• Imaging

  • U/S shows no IVC collapse (euvolemic)

  • Consider CXR to evaluate for pneumonia

• Treatment

  • D/c medications associated with SIADH

  • Fluid restrict to 1.5L daily

  • If no improvement with fluid restriction

    1. Obtain ACTH stimulation test to r/o adrenal insufficiency

    2. ACTH stimulation test negative for adrenal insufficiency: Obtain renal consult and consider starting vaptans

• Pt counseled that long-term control may require loop diuretics and high salt diet

Notes

• Diuretic use and low sodium diets can complicate differentiating between hypovolemic and euvolemic hyponatremia

• Conditions commonly associated with SIADH

  • Surgery

  • Pneumonia

  • CNS insults (e.g. tumor, meningitis)

• Other euvolemic hyponatremia etiologies include hypothyroidism, adrenal insufficiency, Ecstasy use

Hypothyroidism

Primary Hypothyroidism

49 y/o F with h/o HTN, hyperlipidemia, recurrent miscarriages presents with chronic fatigue and cold intolerance. Reports h/o autoimmune disease, ovulatory/menstrual dysfunction, and neck irradiation. Denies currently being pregnant. ROS positive for poor concentration, depression, and diffuse muscle pain. Medications include amiodarone and lithium. Hair thinning, goiter, proximal muscle weakness, lower extremity edema, dry skin, and delayed deep tendon reflexes on exam.

• TSH > 10 mIU/L with low free T4

• Start levothyroxine 1.6 mcg/kg/day PO and repeat TSH testing in 6 weeks

  • Adjust levothyroxine dose every six weeks until TSH within reference range

• Levothyroxine counseling

  • Take every morning on an empty stomach at least 30 minutes before food

  • Do not take within 4 hours of calcium, iron, and/or bile acid sequestrants (e.g. cholestyramine)

Notes

• Initial workup

  • Fatigue and cold intolerance are the most common symptoms of hypothyroidism

  • May be preceded by signs/symptoms of hyperthyroidism, i.e. Hashimoto’s thyroiditis. In these cases, autoimmune destruction of the thyroid gland leads to chronic hypothyroidism.

  • Amiodarone and lithium may cause thyroid dysfunction

  • Start with TSH testing

    • General reference range is 0.5 < TSH < 10 mIU/L

    • If TSH > 5.5 mIU/L, obtain free T4

• Treatment

  • TSH < 10 mIU/L and normal free T4 indicates subclinical hypothyroidism (see vignette/chart below)

  • Hypothyroidism treatment depends on age, symptoms, and pregnancy status

    • For patients 50 or older, start levothyroxine 25 mcg daily and increase by 25 mcg every 4 weeks until TSH reaches desired range

    • In newly pregnant patients, increase current levothyroxine from 7 to 9 tablets weekly (e.g. two tablets on Tuesday/Thursday and one tablet as usual on other days)

• TSH changes in previously stable hypothyroid patients being treated with levothyroxine:

  • Numerous medications may alter TSH, including SSRIs

  • Decreased levothyroxine absorption may occur with atrophic gastritis, chronic PPI use, and/or H. Pylori infection

Subclinical Hypothyroidism

69 y/o F with h/o autoimmune disease and neck irradiation presents with chronic fatigue and cold intolerance. Denies weight gain, constipation, arthralgias/myalgias, weakness, difficulty concentrating, depression. Vital signs WNL. Normal hair, thyroid, and skin on exam.

• TSH 6.9 mIU/L with normal free T4

• Obtain lipid panel, anti-thyroid peroxidase antibodies

• Treat as indicated per laboratory results

Notes

• Subclinical hypothyroidism = elevated TSH with normal free T4

• Treatment depends on age, symptoms, TSH, anti-TPO antibodies, and lipid panel (see below)

• Rule of 7’s: TSH 7 mIU/L or greater and

  • 70+ y/o = treat if symptomatic

  • Less than 70 y/o = treat

Graves Disease

Pregnant pt with h/o autoimmune disease presents with worsening heat intolerance, insomnia, and anxiety/restlessness. Reports recent onset diplopia, blurred vision, reduced color perception, and diarrhea. HTN, exophthalmos, goiter, periorbital edema, thyroid acropachy, pretibial myxedema, and vitiligo on exam.

• TSH < 0.1 mIU/L with inappropriately elevated free T4 and total T3 levels

• Positive anti-thyroid peroxidase (TPO) antibodies

• Radioactive iodine uptake scan of thyroid shows high uptake with homogeneous radioactive iodine distribution

• Treatment

  • 1st trimester of pregnancy: Start Propylthiouracil 50 mg TID and titrate to appropriate TSH

  • After 1st trimester: Methimazole 5-120mg in divided doses; pt counseled about dose-dependent risk for agranulocytosis

• Pt advised that definitive treatment will include radioactive iodine ablation vs. surgical removal of thyroid gland

Notes

• Thyroid acropachy

  • Clubbing of fingers/toes with swelling of hands/feet; considered pathognomonic for Graves disease

  • Rare: Occurs in only 0.3% of patients

• Anti-thyroperoxidase (TPO) antibodies are markers of autoimmune destruction of thyroid tissue may be positive in Graves disease (hyperthyroidism) or Hashimoto’s thyroiditis (hypothyroidism)

• Only hyperthyroid state with high, homogeneous uptake of radioactive iodine

Toxic Multinodular Goiter

Elderly pt presents with new onset palpitations and heat intolerance. Reports associated sweating, tremor, and anxiety. Pt has lived in Great Lakes region her entire life, keeps Kosher, and exclusively eats garden non-processed foods flavored with sea salt. Tachycardia and lid-lag on exam.

• TSH < 0.1 mIU/L with elevated free T4 and T3 levels

• Radioactive iodine uptake scan of the thyroid shows high uptake with nodular radioactive iodine distribution in multiple areas of accumulation

• Treatment: Trial of medications to control symptoms including

  • Propranolol extended release 80 mg daily

  • Methimazole 5 mg TID; f/u labs in 6 weeks with titration to 20 mg TID as needed to maintain TSH, free T4 and T3 in appropriate ranges

• Pt advised about risk for thyroid storm; instructed to contact provider for new onset fever, agitation, tachycardia, irregular heartbeat, diarrhea, and/or pedal edema

Notes

• Second most common cause of hyperthyroidism after Graves disease

  • Pathophysiology: Hyperplasia of thyroid follicular cells that no longer respond to regulation by TSH

  • Most common in elderly patients living in iodine-deficient areas, e.g. those surrounding the Great Lakes in the United States (chronic iodine insufficiency = increased risk for hyperplasia)

  • Most salt in the U.S. is iodized, but unprocessed Kosher or “sea salts” may not contain iodine

• A single toxic adenoma is referred to as Plummer disease; it will present as a single area of accumulation on radioactive iodine uptake scan

Transient Thyroiditis

Pt with h/o autoimmune disease s/p delivery presents with new onset episodes of palpitations and heat intolerance. Recently started on amiodarone, lithium. No goiter, thyroid tenderness, Graves' ophthalmopathy or pretibial myxedema on exam.

• TSH > 0.1 mIU/L but < 0.4 mIU/L with elevated free T4 and T3 levels

• Obtain anti-thyroperoxidase antibodies

• Radioactive iodine uptake scan shows low uptake

• Pt counseled that condition may progress to hypothyroidism

• Pt encouraged to establish appointment with cardiologist and psychiatrist to discuss discontinuing amiodarone and lithium

• Pt advised to follow-up for repeat TSH, FT4, and T3 testing in 6 weeks and again at 6 months

Notes

• May be initiated by

  • Idiopathic autoimmune event (painless)

  • Childbirth (postpartum thyroiditis)

  • Medications, e.g. amiodarone, lithium

• Categories of transient thyroiditis

  • Painless thyroiditis - May or may not be followed by hypothyroidism.

  • Hashimoto’s thyroiditis - Involves autoimmune destruction of thyroid gland that releases thyroid hormone; ultimately followed by hypothyroidism

  • Postpartum thyroiditis - Transient thyroiditis that occurs within 1 year postpartum

• Diagnosis

  • Presence of anti-thyroperoxidase antibodies may indicate Hashimoto’s thyroiditis, but does not rule out Graves disease as they can be present in both conditions

  • A radioiodine thyroid scan may not be indicated in patients with a TSH > 0.1 mIU/L; follow-up with repeat laboratory testing is generally indicated

Subacute (de Quervain) Thyroiditis

Pt with h/o recent viral illness presents with acute onset thyroid tenderness. Reports recent fever. Pain with palpation of thyroid and vesicular rash present on posterior pharynx/hand/feet on exam.

• TSH > 0.1 mIU/L but < 0.4 mIU/L with elevated free T4 and T3 levels

• Obtain anti-thyroperoxidase antibodies

• Radioactive iodine uptake scan shows low uptake

• Naproxen 500 mg BID for pain and inflammation

• Pt cousled that condition generally improves at 6 weeks and resolves at 6 months

• Pt advised to present for repeat TSH, free T4, and T3 testing in 6 weeks and at 6 months

Notes

• Etiology

  • Inflammation due to viral illness releases preformed T4 and T3 hormone

  • Cases have been associated with Coxsackie disease, however, adults may not display the classic viral exanthem

• Presence of anti-thyroperoxidase antibodies indicates autoimmune etiology, i.e. the condition is due to transient instead of subacute thyroiditis 

 Thyroid Nodule Evaluation

Hypoparathyroidism

Pt with h/o autoimmune disorders s/p neck surgery presents with tetany, seizures. Not actively seizing; reports recent paresthesias, emotional lability, anxiety/depression, and difficulty focusing. Hypotension, cataract, irregular heartbeat, positive Chvostek/Trousseau sign, lower extremity edema, and dry skin on exam.

• Labs

  • CMP shows hypocalcemia with normal albumin

  • PTH level inappropriately low in the setting of hypocalcemia

  • Obtain repeat CMP; if repeat level is low

    • Obtain serum ionized calcium

    • Obtain serum 25-hydroxyvitamin D and magnesium levels to rule out alternate causes of hypocalcemia

• EKG shows QTc > 500 milliseconds

• Administer 2g calcium gluconate over 30 minutes; replete to corrected calcium level of 8.0 (see notes for further repletion options)

Notes

• Etiologies

  • Most common: Parathyroid damage during neck surgery

  • Autoimmune destruction of parathyroid glands

• Potential signs/symptoms of hypocalcemia include cataract, arrhythmia, refractory heart failure (edema), tetany, seizures, altered mental status

• PTH and serum calcium

  • Corrected Ca = [0.8 x (normal albumin - patient's albumin)] + serum Ca

  • Normal PTH level = 10-65 mg/dL

  • Normal PTH in setting of low calcium also indicates hypoparathyroidism

• Calcium repletion

  • 1g calcium is equivalent to

    • CaCO3 250 mg PO

    • Calcium gluconate 1g IV over 30 minutes

  • Corrected calcium < 7.5 mg/dL with arrhythmia and/or seizure:

    • Start 2g IV calcium over 30 minutes

    • Notify ICU as transfer may be necessary if symptoms do not resolve. (Administering greater than 2g of calcium over 30 minutes requires a central line.)

    • Repeat CMP in 4 hours

  • Corrected calcium < 7.5 mg/dL with mild symptoms (e.g. paresthesias) and/or QTc > 500 milliseconds but no arrhythmia:

    • Obtain serum ionized calcium to confirm hypocalcemia

    • Administer 1g calcium (preferably PO) and repeat CMP in 12 hours

  • 7.5 or greater and no symptoms: Consider starting 1g calcium carbonate PO and monitor with daily CMP

Primary Hyperparathyroidism

55 y/o F with h/o neck radiation, nephrolithiasis, long-bone fractures presents, bipolar disorder for health maintenance exam. Reports intermittent lethargy/fatigue, weakness, epigastric pain, nausea/vomiting, insomnia, and forgetfulness. Medications include lithium. Hypertension, irregular heartbeat, abdominal tenderness, flank pain, muscle weakness, and lower extremity edema on exam.

• CMP shows hypercalcemia

  • Repeat CMP and re-evaluate serum calcium and creatinine levels

  • If repeat serum calcium elevated, obtain serum ionized calcium

• Obtain serum vitamin D, magnesium, and lithium levels

• PTH > 65 mg/dL in setting of hypercalcemia: Obtain 24-hour urine calcium:urine creatinine ratio

  1. Ratio > 0.01: Primary hyperparathyroidism confirmed

     • Obtain Sestamibi scan to confirm hyperparathyroidism due to excess parathyroid activity and refer for surgical removal of parathyroid glands pending positive scan

     • Consider genetic analysis for MEN syndrome

  2. Ratio 0.01 or less: Diagnose familial hypocalciuric hypercalcemia (see notes below)

Notes

• Risk factors include female sex, age > 50 years, and h/o neck radiation

• Presentation

  • Most patients are asymptomatic at diagnosis

  • Elements of the classic stones (nephrolithiasis), bones (osteitis fibrosa cystica), groans (abdominal pain due to pancreatitis), and psychiatric overtones (lethargy/fatigue, weakness, insomnia, impaired memory) may be present

  • Hyperparathyroidism is sometimes associated with hypertension, arrhythmia, heart failure, and muscle weakness

• Diagnosis

  • Primary hyperparathyroidism is most commonly an incidental diagnosis

    • Low vitamin D and/or calcium levels may cause hypoglycemia and lead to elevated parathyroid hormone in the setting of low to normal calcium values

    • Lithium can raise PTH levels, thereby causing hypercalcemia; chronic use may also lead to renal failure and associated hypocalcemia due to decreased vitamin D production

  • Familial hypocalciuric hypercalcemia

    • This condition is due a “calcium sensor that reads low.” In other words, a normal sensor shuts off PTH when the calcium level reaches ~9.0 mg/dL, i.e. normal. In patients with familial hypocalciuric hypercalcemia, the sensor doesn’t activate until calcium levels reach ~11.0 or higher, i.e. elevated.

    • Patients may not need surgical removal of parathyroid glands if they are not displaying signs/symptoms of hyperparathyroidism

  • If PTH is low, primary hyperparathyroidism is ruled out: Obtain 25-hydroxyvitamin D, 1,25-hydroxyvitamin D, and PTH-rP level to evaluate for parathyroid-independent causes of hypercalcemia

Secondary Hyperparathyroidism

Pt with h/o chronic kidney disease, bipolar disorder controlled with lithium, and h/o gastric bypass surgery presents with hypocalcemia. Reports recent paresthesias, emotional lability, anxiety/depression, and difficulty focusing. Hypotension, cataract, lower extremity edema, positive Chvostek/Trousseau sign, and dry skin on exam.

• Labs

  • CMP shows hypocalcemia with normal albumin

    • Obtain repeat CMP

    • If repeat CMP shows hypocalcemia, obtain serum ionized calcium

  • PTH > 65 mg/dL

  • Obtain 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 levels

• Obtain EKG and evaluate QTc

• Start vitamin D and/or calcium supplementation as needed to prevent osteomalacia

• Pt counseled about importance of vitamin supplementation s/p bariatric surgery

Notes

• Etiology

  • Renal failure = most common etiology

    • May occur due to chronic lithium use

    • Decreases conversion of 25-hydroxyvitamin D3 to the active 1,25-dihydroxyvitamin D3

  • May be related to decreased vitamin D and/or calcium absorption, e.g. due gastric bypass surgery

  • Insufficient calcium intake is rare in developed nations

• Normal values

  • PTH 10-65 mg/dL

  • 25-hydroxyvitamin D > 10 ng/mL 

Obesity/Weight Loss

Patient with history of DM type 2, HTN, HLD, obstructive sleep apnea, non-alcoholic fatty liver disease presents due to weight gain. Patient is unhappy with her current weight. Does not exercise and reports inadequate fruit/vegetable consumption. Greater than 25% of calories consumed between evening meal and breakfast. Reports changes in routine leading to change in location where food is purchased, increased sedentary behavior, increased screen time, sleep deprivation. Medications include amlodipine, sulfonylureas, thiazolidinediones, amitriptyline, mirtazapine, paroxetine, antipsychotics. BMI > 30 kg/m^2.

• Obtain TSH, HbA1c

• Counseling

  • Diet

    • No diet has been shown to be superior for weight loss provided it reduces the number of calories consumed per day

    • Select a diet that is sustainable and, ideally, increases fruit and vegetable consumption

    • Reduce intake of beverages containing sugar, alcohol

    • Do not consume fewer than 800 Calories per day without medical supervision

  • Exercise: CDC recommends 150 minutes of moderate exercise per week including 2 days of strength training that work all major muscle groups

  • Additional risk factors for weight gain

    • Discount foods that often contain added sugar, salt

    • Night eating syndrome: Greater than 25% of calories consumed between evening meal and breakfast

    • Small changes in physical activity, e.g. energy saving appliances, decrease in vigorous physical activity by as little as 5-10 minutes per day

    • Increased screen time leading to sedentary behavior +/- inadvertent calorie consumption

  • Factors with minimal impact on overall weight (~5 pound weight gain or less): Healthy pregnancy, oral contraceptives

• Initial interventions

  • Calculate current BMI and target weight

  • Substitute weight neutral medications if possible (see notes)

  • Perform motivational interviewing concerning healthy lifestyle changes

  • Log calorie consumption and exercise habits x 1 week and follow-up to review results

  • Consider medical/surgical therapy (see below) after instituting lifestyle change and ruling out other medical disorders (see below)

Medical Disorders Associated with Weight Gain

Polycystic Ovarian Syndrome (PCOS)

Cushing disease

• Physical exam: Facial erythema, buffalo hump, abdominal stretch marks, bruising, and thin arms/legs

• Verify no exogenous glucocorticoids

• Concern for diagnosis per physical exam: Obtain 24-hour urinary free cortisol (UFC) excretion x 2 measurements

Binge eating disorder

• Criteria (DSM 5)

  • Recurrent and persistent episodes of binge eating associated with three (or more) of the following: Eating much more rapidly than normal, eating until feeling uncomfortably full, eating large amounts of food when not feeling physically hungry, eating alone because of being embarrassed by how much one is eating, feeling disgusted with oneself/depressed/very guilty after overeating

  • Marked distress regarding binge eating

  • Absence of regular compensatory behaviors (such as purging)

• Treatment

  • Refer for counseling

  • Start escitalopram 10 mg daily and increase to 20 mg daily after 1 week

Medical/Surgical Therapy for Persistent Obesity

• BMI > 30 with < 5% weight loss after 6 months: Consider oral therapy

  • History of DM: Start liraglutide 0.6 mg sub-Q daily and increase dose by 0.6 mg at weekly intervals until reaching maximum dose of 3 mg qd

  • No history of DM and

    • No cardiovascular risk factors: Start phentermine-topiramate 3.75-23 mg daily x 14 days. Increase to 7.5-46 mg daily x 12 weeks before re-evaluating weight loss. Discontinue if < 3% weight loss during that time.

    • Cardiovascular risk factors: Start lorcaserin 10 mg BID and re-evaluate after 12 weeks. Patient counseled about risk of anal leakage with medication.

• BMI > 40: Discuss referral to bariatric surgery program

Notes

• Obesity classification based on BMI (kg per m^2): Class 1 (30.0-34.9), Class 2 (35.0-39.9), Class 3 (40 or greater)

• Complications of obesity include DM type 2, HTN, HLD, obstructive sleep apnea, non-alcoholic fatty liver disease

• Medication classes associated with weight gain and alternatives

  • Antidepressants

    • Promote weight gain: Amitriptyline, mirtazapine, paroxetine

    • Weight neutral: Most SSRIs, e.g. escitalopram, fluoxetine

    • Promote weight loss: Bupropion

  • Weight neutral antipsychotics: Aripiprazole (Abilify), haloperidol, and ziprasidone (Geodon)

  • Mood stabilizers: Lithium promotes weight gain while oxcarbazepine is weight neutral

  • Blood pressure agents: Amlodipine promotes weight gain while ACE inhibitors are weight neutral

  • Diabetes medications

• Treatment

  • Consider drug therapy in the following cases

    • BMI of 30 or greater

    • BMI of 27 or greater with cardiovascular comorbidities

    • Failure to lose 5% of total body weight after 3-6 months of comprehensive lifestyle change

  • Weight loss medications

    • Phentermine-topiramate has greater efficacy that lorcaserin or liraglutide but comes with increased cardiovascular risk.

    • Orlistat 120 mg TID with fat-containing meals is another option with efficacy similar to that of lorcaserin; drawbacks include anal leakage. Patients should avoid wearing white pants when taking the medications.

  • Bariatric surgery (see below)

• Bariatric surgery

  • Without bariatric surgery, annual probability of achieving BMI < 30 in patient with BMI 40 to 44.9 is 1 in 1290 for men and 1 in 677 for women (JAMA 2017)

  • Relatively safe and reduces obesity-related conditions, e.g. all-cause mortality, myocardial infarction, stroke

  • Post-surgical care

    • Bariatric multivitamin, ferrous gluconate 240 mg [elemental iron 27 mg] daily

    • Evaluate for nutrient deficiencies every 3 months for 1 year and then yearly: Obtain CBC, TIBC, ferritin, B1, B12, folate, 25(OH) vitamin D, zinc, copper

Diabetes Mellitus Type I

5 y/o M with h/o prolonged candida infections presents with acute onset lethargy, polyuria, and polydipsia. Parents report family h/o DM type 1. Weight loss noted on exam.

• Labs

  • Urine positive for ketones

  • BMP shows plasma glucose > 200 mg/dL

  • Positive autoantibodies to islet cells, insulin, glutamic acid decarboxylase, insulinoma-associated antigen-2, and zinc transporter 8

  • Obtain TSH to screen for concomitant thyroid disease; if abnormal test for antithyroid peroxidase and antithyroglobulin antibodies

• Treatment

  • Stabilize pt according to DKA protocol

  • Initiate basal insulin glargine at 0.1 u/kg/day and follow-up fingersticks in 1 week; increase dose by 10% weekly until morning fingerstick glucose consistently < 130 but > 90 u/dL

  • Start 0.1 u/kg/day short acting insulin aspart divided between breakfast, lunch and dinner; adjust by 10% weekly until preprandial fingerstick glucose < 130 but > 90 u/dL

• Education

  • Parents and pt educated about insulin injection

  • Parents and pt educated about pre-meal and pre-bedtime fingerstick glucose monitoring with goals of 90-130 mg/dL and 90-150 mg/dL, respectively

  • Parents counseled that failure to adhere to insulin regimen may result in blindness, heart/vascular disease, kidney failure, and/or limb amputation

• Follow up as outpatient

  • Monitor for development of HTN

  • Consider starting lisinopril if urine albumin-to-creatinine ratio > 30 mg/g

  • Starting at age 10 years

    • Obtain lipid profile; start statin if LDL > 160 mg/dL

    • Perform yearly foot exam

  • Refer for yearly ophthalmology exams

  • Consider referral for insulin pump

Notes

• Onset has a bimodal distribution with peaks occurring at age 4-6 years and 10-14 years

• HbA1c

  • HbA1c may be inaccurate if onset occurred fewer than 3 months ago; obtain BMP

  • Long term HbA1c goal in pediatric patients is less than 7.5%

• Increased risk for other autoimmune diseases:

  • Consider screening for Celiac disease if presenting with diarrhea

  • Also consider Addison’s disease, autoimmune hepatitis, and/or myasthenia gravis if associated symptoms develop

• Renal disease

  • Monitor for development with yearly urinary albumin-to-creatinine ratio

  • Most common cause of hypoglycemia in previously controlled DM I

Diabetes Mellitus Type 2

Non-caucasian patient < 65 years with h/o schizophrenia, NAFL, PCOS, gestational diabetes presents for health maintenance exam. ROS positive for fatigue, blurry vision, polyuria/polydipsia, and numbness/tingling in the lower extremities. BP > 140/90, acanthosis nigricans, and foot ulcer on exam.

Initial Labs

• No h/o asplenia, anemia, or recent acute blood loss with HbA1c > 6.4%

• Obtain lipid panel

HbA1c and Associated Therapy

• HbA1c < 9%

  • GFR > 30: Start metformin and recheck HbA1c every 3-6 months

  • If follow-up HbA1c > 7%, add up to 2 additional oral agents before starting insulin (see HbA1c > 9%)

• HbA1c 9-10%: Initiate metformin and empagliflozin (Jardiance); pt counseled about risk for UTI/pancreatitis and need for repeat HbA1c in 3 months

  • HbA1c > 7% after 3 months: Start liraglutide (Victoza) and recheck HbA1c in 3 months

  • HbA1c > 7% after 3 months on 3 oral agents: Start insulin (see HbA1c > 10%)

• Initial HbA1c > 10%

  • Initiate basal insulin glargine (Lantus) at 0.1 u/kg/day

    • Initiate finger-stick log and follow-up in 1 week

    • Increase dose by 10% weekly until morning fingerstick glucose consistently < 130 but > 80 mg/dL

    • Titrate to to 0.4-1.0 u/kg/day until morning fingerstick goals are achieved and decrease by 10% for hypoglycemic events (morning fingerstick < 70)

    • Maximum daily dose 200 units/day

  • If HbA1c > 7% after 3 months: Start 0.1 u/kg/day short acting insulin aspart (Novolog) divided between breakfast, lunch and dinner (e.g. 120 kg = 12u = 4u at each meal). Adjust by 10% weekly until preprandial fingerstick glucose < 130 but > 80 mg/dL.

• Monitor HbA1c every 3-6 months

• Obtain microalbumin-to-creatinine ratio and perform foot exam yearly

Additional Treatment

• Stain therapy

  • ASCVD < 7.5%: Start rosuvastatin 10mg

  • ASCVD > 7.5%: Start rosuvastatin 20mg

• Administer pneumococcal vaccine (PPSV23)

Counseling

• Refer pt for intensive behavioral counseling interventions focusing on diet/exercise

• Pt advised that failure to adhere to therapy may result in blindness, cardiovascular disease, kidney failure, and/or limb amputation

Notes

• 2019 ADA Guidelines for Primary Care Providers

• Patients at increased risk for developing diabetes

  • Member of ethnic groups including Asian, black, Hispanic, Native American/Pacific Islander

  • Use of antipsychotics

  • HbA1c value of 5.7 to 6.4% (“pre-diabetes”)

• Screening

  • Screen patients age 40 to 70 years who with BMI 25.0 or greater; repeat every 3 years if results are normal

  • Screening may be considered in patients under 40 with BMI > 85th percentile or those with risk factors such as ethnicity, family history, PCOS, HTN, and/or HLD

  • Positive screen includes one of the following

    • HbA1C level > 6.4%

    • Fasting plasma glucose 126 mg/dL or greater

    • Plasma glucose 200 mg/dL or greater for fasting level and/or 75 g 2-hour glucose tolerance test

• HbA1c

  • HbA1c goals

    • Age less than 65: Goal < 7.0%

    • Age 65 or greater: Goal 7.0 to 7.9%

  • HbA1c assumes RBC lifespan of approximately 3 months

    • Falsely low values occur with hemolytic anemias, acute blood loss

    • Falsely elevated values occur with asplenia, iron deficiency/aplastic anemias

  • Cannot be used in pregnancy (see gestational DM)

• Fingerstick glucose goals

  • Home

    • Morning fingerstick glucose: 70-100 mg/dL

    • Preprandial: 80-130 mg/dL

  • Hospital fingerstick glucose: 140-180 mg/dL

• Non-insulin medications

  • Metformin

    • Contraindicated in patients with GFR < 30 mL/minute/1.73 m^2

    • Once initiated, should be continued as long as tolerated; additional agents including insulin should be added to metformin (ADA Guidelines)

    • May lower B12; check levels periodically, especially if anemia or peripheral neuropathy develops

  • If empagliflozin or liraglutide not tolerated, start pioglitazone

  • See DM type 2 medications for more information

Diabetic Ketoacidosis

Pt with h/o DM type 1 presents with sub-acute onset of polyuria/polydipsia with concomitant weight loss, fatigue, dyspnea, N/V, abdominal pain, polyphagia. Reports recent pneumonia, UTI, cocaine/alcohol abuse. Medications include second generation antipsychotics. Has not been taking insulin as instructed due to pump failure, financial issues, confusion about insulin regimen. Febrile and stuporous with dry mucous membranes on exam. Initial labs show serum bicarbonate < 18 mEq/L, glucose > 250 mg/dL, anion gap (AG) > 16 mEq/L, serum osmolality > 320, pH on ABG < 7.3.

• Labs

  • Obtain CBC, CMP, ABG, U/A

  • Obtain serum beta-hydroxybutyrate, amylase, lipase, lactic acid, creatinine kinase

  • Obtain HbA1c if not performed within previous 3 months

  • Timed

    • Obtain BMP, phosphorus, magnesium q4 hours until AG < 12

    • Obtain fingerstick glucose q1 hour x 4

    • Report intake and output q4 hours

• IV fluid

  • Initial progression

    • Normal saline (0.9%) at 1 L/h x 1h, then 500 mL/h x 2h then

    • 0.45% saline at 500 mL/h x 2h then

    • 0.45% saline at 200 mL/h maintenance

  • When WBG < 250 mg/dL, start D5 0.45% saline at 200 mL/hr

• If initial potassium

  • 4 to 5.2: Infuse KCl at 10 mEq/h IV x 2h

  • 3.3 to 4: Infuse KCl at 10 mEq/hr IV x 3h

  • 3.2 or lower: Replete as appropriate and start KCl at 10 mEq/hr IV x 3h

• Insulin

  • Start insulin infusion at 0.1 u/kg/h; max 10 u/h

    • When WBG < 250 mg/dL and decreased 100 mg/dL from starting value, decrease infusion rate by half and recheck WBG in 30 min

    • When WBG < 200 mg/dL and decreased 60 mg/dL in previous 2 hours, decrease insulin rate by half

    • When WBG <100mg/dL, decrease insulin rate by half and change to D10 0.45% saline at current rate

  • Administer long-acting insulin SQ when AG < 12 and serum CO2 > 14

  • Continue insulin infusion for 30 minutes after starting long acting insulin

• Additional evaluation and treatment

  • Obtain EKG

  • Zofran 4 mg IV q8h PRN for nausea

  • Monitor for s/sx of cerebral edema

• Pt's family advised that fatality rate is up to 5%

• Educate pt and family about insulin adjustment during illness, blood glucose monitoring, and importance of medication compliance

Notes

• Febrile illness precedes 40% of DKA cases

• AG = anion gap = Na - (Cl + CO2)

• Serum osmolality = 2(Na + K) + (glucose/18) + (blood urea nitrogen/2.8)

• Bicarbonate therapy is has not be shown to improve outcomes

• Rule out

  • 10-15% of DKA patients have concomitant pancreatitis; rule in/out with serum amylase, lipase

  • Other high anion-gap metabolic acidosis, e.g. lactic acidosis, uremia, rhabdomyolysis, toxic alcohol ingestion (alcohol, ethylene glycol, methanol)

HHS

diagnosis = serum glucose >600, osmolarity >300, absent/minimal ketonse, arterial pH>7.3, serum bicarb>20
-high flow NS; add dextrose 5% when WBG <200
-serum potassium <= 5.2; add IV potassium
-serum potassium >=3.3; start initial continuous insulin infusion
-consider bicarbonate if pH < 6.9
-consider phosphate for serum phosphate <1.0 mg/dL, cardiac dysfunction, respiratory depression
-frequent monitoring of serum Ca
-tolerates PO intake, WBG<200mg/dL, anion gap<12 and serum HCO3 >15; d/c start SQ basal bolus insulin and d/c IV insulin in 1-2 hours
(true for DKA as well)

Rheumatoid Arthritis (RA)

45 y/o F with h/o smoking presents with pain/stiffness in the proximal interphalangeal/metacarpophalangeal joints, wrists, and knees. Reports fatigue, weight loss, dry eyes, dry mouth, SOB, and morning stiffness in affected joints lasting greater than 1 hour. Denies distal interphalangeal joint pain, lumbar spine pain. Reports family h/o rheumatic disease, including RA. Conjunctival injection, joint swelling of PIPs, and rheumatoid nodules on exam.

• Obtain ESR, CRP, IgM rheumatoid factor, and anti-citrullinated protein antibody level

• Obtain CBC to rule out anemia

• Screen for hepatitis B/C and tuberculosis if not already performed

• Treatment

  • Start methotrexate 10 mg once weekly; increased by 5 mg every 4 weeks to maximum dose of 20 mg once weekly

  • Symptom resolution not achieved with 20 mg weekly; refer to rheumatology

• Pt informed that DMARD may be tapered or discontinued once 6 months of symptom remission is achieved

• Pt counseled that symptom remission with methotrexate monotherapy is only achieved in approximately 40% of patients

Notes

• Earlier diagnosis and treatment of RA with disease-modifying antirheumatic drugs (DMARDs) dramatically improves outcomes

  • Mean age at onset: 48 years

  • Rheumatoid nodules and radiographic erosive changes are no longer criteria for diagnosis

  • Differential includes systemic lupus erythematosus, systemic sclerosis, psoriatic arthritis, sarcoidosis, crystal arthropathy, and spondyloarthropathy

• Extra-articular manifestations

  • Include keratoconjunctivitis sicca, interstitial lung disease, and pleural effusions

  • May manifest as complaints of eye redness, dry eyes, dry mouth, and/or SOB

• Methotrexate

  • Patients must be screened for hepatitis and tuberculosis before starting DMARDs

  • Toxicity risk increases with doses greater than 20 mg weekly

Polymyalgia Rheumatica

70 y/o white F with h/o carpal tunnel syndrome presents with gradual onset b/l pain in shoulders, neck, and hips. Reports fatigue, weakness, low-grade fever, morning stiffness lasting >45 minutes, and myalgias/arthralgias that are worse at night. Denies abrupt onset headache, tongue/jaw claudication. Weight loss, proximal joint pain, proximal muscle weakness, asymmetric arthritis in wrist/knees, pitting edema of wrists/ankles on exam.

• Labs

  • ESR > 40 mm/hr

  • CBC shows mild anemia, thrombocytosis

  • Obtain CMP, TSH, CRP, creatinine kinase, rheumatoid factor, urinalysis, and protein electrophoresis to rule out mimics, including paraneoplastic syndrome

• Obtain DEXA scan prior to starting corticosteroid therapy

• Treatment

  • Start prednisone taper: 15 mg qd x3 weeks, then 12.5 mg qd x3 weeks, then 10 mg qd x5 weeks, then decrease by 1 mg every 5 weeks as tolerated

  • Pt on long-term corticosteroid therapy: Prophylax with alendronate 35 mg q weekly to preserve bone mineral density and reduce fracture risk

• Pt counseled that the average length of treatment with steroids is 2 years and that relapses requiring repeat courses may occur

• Pt counseled about long-term risks of corticosteroid use including peptic ulcers and loss of bone mineral density

Notes

• Most common chronic inflammatory condition in older adults

• Affects ~1 in 140 people of European descent >50 y/o

• Giant cell (temporal) arteritis

  • Occurs in up to 25% of polymyalgia rheumatica cases

  • Red flags: Sudden onset headache, jaw/tongue claudication, ESR >100 mm/hr

  • Treatment: Prednisone 60 mg qd, ophthalmology consult +/- temporal artery biopsy

• Associated tenosynovitis may produce carpal tunnel syndrome

Polymyositis and Dermatomyositis

45 y/o F pt with h/o atopy presents with gradual onset muscle weakness. Weakness particularly noticeable when climbing stairs, rising from seated position, and/or picking up heavy objects, e.g. groceries. ROS positive for dysphagia, SOB. Physical exam reveals faint pulmonary crackles, proximal muscle atrophy/weakness affecting deltoids/hip flexors, hyperkeratotic/fissured skin on palmar surfaces (mechanic’s hands). [Gottron’s papules, heliotrope eruption present.]

• Labs

  • Obtain CBC, CMP, creatine kinase (CK) and lactate dehydrogenase (LDH) levels

  • Obtain antinuclear antibodies; if positive

    • Obtain anti-Jo-1 antibodies

    • Consider obtaining anti-Ro, anti-La, anti-Sm, anti-RNP antibodies

  • Concern for heart disease: Obtain CK-MB

• Imaging

  • EKG shows non-specific conduction abnormalities

  • CXR shows interstitial opacities suspicious for interstitial lung disease

  • MRI shows widespread muscle inflammation, fibrosis, calcification

• Muscle biopsy shows lymphocytic infiltrate

• Treatment: Refer/consult rheumatology

  • Unstable: Admit to hospital, start methylprednisolone IV 1000 mg/day

  • Stable

    • Start 1 mg/kg prednisone daily (max dose 80 mg/day)

    • Consider transitioning to azathioprine 50 mg/day for long-term therapy

• Pt counseled about risks of immunosuppressive therapy

Notes

• Prevalence = 2 in 100,000

• Skin changes

  • Nonspecific findings, e.g. mechanic’s hands occur in both disorders

  • Shawl sign: Poikiloderma in sun exposed areas (e.g. upper back, chest) sometimes found in dermatomyositis patients

  • Gottron’s papules/heliotrope eruptions are pathognomonic for dermatomyositis

    • Gottron’s papules: Symmetrical violaceous lesions on extensor surfaces

    • Heliotrope eruption: Symmetrical violaceous eruption on the upper eyelids

• Additional clinical manifestations

  • Interstitial lung disease affects 10% of patients

  • Damaged cardiac muscle may produce conduction abnormalities on EKG

  • Dysphagia may occur due to oropharyngeal muscle weakness

• Diagnostic testing

  • Presence of anti-Ro, anti-La, anti-Sm, or anti-RNP antibodies may indicate presence of other autoimmune conditions

  • MRI is sensitive, but not specific

  • Muscle biopsy showing perifascicular atrophy is pathognomonic for dermatomyositis