Diabetes & Thyroidreviews.berlinpharm.com/20180505/DM Thyroid ASCE.pdf · อ้วน...

Diabetes & Thyroid

OPD Case Management

Suranut Charoensri, MDDivision of Endocrinology and Metabolism

Department of Medicine

Faculty of Medicine, Khon Kaen University

Consultation : Diabetes

Diagnosis of Diabetes

แนวทางเวชปฏบตส าหรบโรคเบาหวาน พ.ศ. 2560

มากกวา 8 ชวโมง

หวน าบอย ปสสาวะบอยและมาก น าหนกตวลดลงโดยทไมมสาเหต

ส าหรบผทไมมอาการของโรคเบาหวานชดเจน ควรตรวจเลอดซ าโดยวธเดมอกครงหนงตางวนกน

Four Types of Diabetes


90 – 95%

• DM type 1 Young, lean, severe presentation, DKA

Gradual onset, DKA when precipitated (esp. in adults)

Lab : Low/undetectable C-peptide, positive autoantibodies

• Gestational diabetes (GDM)

• Specific types of DM due to other causesClues: Neonatal onset, strong family history, drugs, pancreatic disease, endocrinopathy, syndromic features

DM type 2Obese, insulin resistant

Gathering Important Data

Nature of Disease

Disease Status

Comorbid & Complications

Types of DM, risks, presentation, duration

Symptoms, current medications, , laboratory results

Other CV risk factors, macrovascular, microvascular

Initial Evaluation


Obesity Evaluation

อวน หมายถง • BMI > 25 กก./ม.2 และ/หรอ • รอบเอว > 90 ซม.ในผชาย หรอ > 80 ซม.ในผหญง หรอมากกวาสวนสงหารดวย 2 ทงสองเพศ


Treatment Checklist

Treatment goal• Individualization

• Good glycemic control + avoid hypoglycemia

Medications

Lifestyle modification

Treat comorbidities and complications

Treatment Goal

Set Glycemic Goal First !


Factors to be considered

Standards of Medical Care in Diabetes - 2018. Diabetes care 2017;41(Suppl. 1)

Medications

Efficacy of non-insulin Medications

* Standards of Medical Care in Diabetes - 2018. Diabetes care 2017;41(Suppl. 1)แนวทางเวชปฏบตส าหรบโรคเบาหวาน พ.ศ. 2560

Metformin

1 – 2 %Sulfonylureas

1 – 2 %

Thiazolidinediones

0.5 – 1.4 %

DPP4 inhibitors

0.6 – 1.0 %

GLP-1 receptor agonists

0.8 – 1.8 %

SGLT2 inhibitors

0.6 – 1.2 %

[HbA1c reduction]

High efficacy

Intermediate efficacy

*

โFPG < 180 mg/dL or A1C < 8 Lifestyle treatment

โFPG > 180 mg/dL or A1C > 8 Metformin unless contraindicatedChoices: SU, TZD, DPP4i

โFPG > 220 mg/dL or A1C > 9Metformin + SU

(or other oral agents)

FPG ≥ 300 mg/dL or A1C > 11 or hyperglycemic symptoms Oral agents

+Basal insulin hs

More complex insulin regimen

3 agentsCurrently on treatment but FPG > 300 mg/dL or

A1C > 11 ± comorbidities

Life

styl

e m

od

ific

atio

n



Basal insulin+

1 Prandial insulin

More complex insulin regimen

Basal insulin+

GLP-1RA

1-2 premixed insulin

Basal insulin + 2-3 Prandial insulin

+ oral agent

Class Advantages Disadvantages

Metformin • High efficacy• Low cost• Weight neutral• Low risk hypoglycemia

• Gastrointestinal side effects (diarrhea, N/V)• Potential for vitamin B12 deficiency• Lactic acidosis (rare)• Contraindicated in GFR < 30 ml/min/1.73 m2

Sulfonylureas • High efficacy• Low cost

• Weight gain• High risk hypoglycemia

Glinides • Rapid acting• Postprandial control

• High cost• High risk hypoglycemia / weight gain

Thiazolidinediones • High efficacy• Low risk hypoglycemia• Benefit in NASH

• Weight gain, fluid retention• Avoid in congestive heart failure• Risk of fractures• ? Bladder cancer

Alpha glucosidase inhibitors

• Postprandial control• Weight neutral

• Contraindicated in GFR < 30 ml/min/1.73 m2

DPP4 inhibitors • Weight neutral• Low risk hypoglycemia

• High cost• Contraindicated in pancreatitis

GLP-1 receptor agonists

• High efficacy• Weight reduction• Low risk hypoglycemia

• Very high cost• Nausea and vomiting• Contraindicated in pancreatitis, medullary CA thyroid

SGLT-2 inhibitors • Weight reduction• Low risk hypoglycemia

• High cost• Avoid in GFR < 45-60 ml/min/1.73 m2

• Risk of GU infections, euglycemic DKA, fractures

Rapid Aspart, Lispro, Glulisine

Short Regular insulin

Intermediate Neutral Protamine Hagedorn (NPH)

Long Glargine U-100, Detemir

Ultralong Degludec, Glargine U-300

Premix Biphasic human 70/30, BiAsp 70/30

Co-formulation IdegAsp, IGlarLixi, IdegLira

Prandial insulin

Basal insulin

Class 15 30 45 60 90

Metformin Avoid ↓ 50% (Max 1,000) Caution Max 2,550 mg/d

Sulfonylurea No dose adjustments

Rapeglinide No dose adjustments

TZDs No dose adjustments

Sitagliptin 25 mg OD 50 mg OD 100 mg OD (GFR > 50)

Saxagliptin 2.5 mg OD 5 mg OD (GFR > 50)

Vidagliptin 50 mg OD 50 mg BID (GFR > 50)

Linagliptin No dose adjustments

Gemigliptin No dose adjustments

Liraglutide Avoid No dose adjustments

Acarbose Avoid No dose adjustments

Canagliflozin Avoid 100 mg OD 100 – 300 mg OD

Dapagliflozin Avoid 5 – 10 mg OD

Empagliflozin Avoid 10 – 25 mg OD

Insulin No dose adjustments

eGFR

CKD Adjustment

Use with caution, beware SE

Lifestyle modification& Diabetic self management

Lifestyle Modification

Weight reduction if BMI increased

• 500 - 750 kcal/day caloric deficit

or

• 1,200 - 1,500 kcal/day for women

• 1,500 - 1,800 kcal/day for men

• Aim > 5% weight reduction

• Sustained weight loss ≥ 7%

Standards of Medical Care in Diabetes - 2018. Diabetes care 2017;41(Suppl. 1)แนวทางเวชปฏบตส าหรบโรคเบาหวาน พ.ศ. 2560

Carbohydrates (Carb)

Type of Carb

• Low glycemic index, glycemic load

• Increase fiber

• Avoid sugar sweetened beverage

• Limit sugar intake

• Also, limit artificial sweetener

Carb counting and Carb exchange

Glycemic load = glycemic index x CHO content100


Glycemic Index

Low GI < 55 , Medium GI 55-69 , High GI > 70

Lipid

Fatty acid

• Saturated fat < 7%

• Trans fat < 1%

• Increase omega-3 fatty acid

Cholesterol

• No recommendations regarding CVD reduction


Saturated fat

Trans fat

Other Key Nutrients

Protein

• Fish and poultry

Na < 2000 mg/day


น ำปลำ 1 ชอนโตะNa = 1,120 – 1,420 mg

ผงชรส 1 ชอนชำNa = 492 mg

เกลอแกง 1 ชอนชำNa = 2,000 mg

ซอว 1 ชอนโตะNa = 960 – 1,420 mg

Exercise


Moderate intensity exercise

• 50 – 70% of max HR (220-age)

• Talk test (able to complete the sentence)

• In elderly• Start from low intensity (< 50% of max HR)

• Slowly titrate → not more than vigorous intensity (>70% max HR)

• 150 minutes/week

• 30 – 50 minutes/day for 3-5 days/week

• No more than 2 consecutive days without activity

• Resistance exercise 2-3 sessions/week

Exercise

Aerobic exercise

Resistance exercise

Other Recommendations


• Stop smoking !

• Alcohol : not recommendedif necessary• 1 drink/day in woman

• 2 drinks/day in man

• Influenza vaccine annually

Whisky 45 ml Beer 330 ml Wine 150 ml

• Injection device and technique

• Self monitoring blood glucose (SMBG)

• Hypoglycemia management

• Sick day management

Diabetes Self Management Education

DSME

Injectable Devices

Vial Penfill

Injectable Devices

Disposable pen

Injection Technique

Injection Sites

Injection Needles

• Repeated use not more than 5 times

• Clean the skin with alcohol at injection site before every injections

Storage

ยาทเปดใชแลว

• แชตเยน (4 oC) ≈ 1 เดอน

• อณหภมหอง (30 oC) ≈ 1 เดอน

ยาทยงไมเปดใช

• แชตเยน (4 oC) วนหมดอาย

• อณหภมหอง (30 oC) ≈ 1 เดอน

Hypoglycemia Management


Hypoglycemia : plasma glucose ≤ 70 mg/dl

Mild hypoglycemia

• Take fast-acting carbohydrate 15 – 30 grams

• Follow capillary glucose level at 15 minutes

• Repeat treatment if the glucose level is still ≤ 70 mg/dl

• After improved, take complex carbohydrate or regular meal to prevent recurrent hypoglycemia

Severe hypoglycemia

• Transfer to the hospital immediately

• During transfer, apply sweet syrup or honey at buccal mucosa

Treat Comorbidities& Complications

Treat Other CV Risk Factors


Hypertension• BP < 140/90 mmHg

• ACEI, ARB → primary prevention of albuminuria

Dyslipidemia• Age ≥ 40 years : moderate intensity statin

• Aim LDL-c < 100 mg/dl or lower than 30%

Stop smoking

Albuminuria (UACR ≥ 30 mg/g)• No HT : ACEI, ARB → slow CKD progression

• HT : ACEI, ARB → slow CKD progression, keep BP < 130/80 mmHg

• GFR < 30 : ACEI, ARB demonstrates risk of AKI, hyperkalemia > benefit

Antiplatelets


Primary prevention of ASCVD

Consider in age ≥ 50 years + 1 other CV risk factor

• Family history of premature ASCVD

• Hypertension

• Dyslipidemia

• Smoking

• Albuminuria

Dose : ASA (75 – 162 mg/day)

Bleeding risk must be considered

Microvascular Complications


Evaluation : T1DM 5 years after diagnosis

T2DM at the time of diagnosis then annually

DR : Fundoscopic examination

DKD : UACR, eGFR

Foot examination • General appearance and deformities• 10-g monofilament• Posterior tibial, dorsalis pedis pulse or ABI

10-g Monofilament Testing


Test : Loss of protective sensation (LOPS) No. 5.07 (10 gm pressure)Demonstrate normality at palm or forearm

Patient is supine or seated position, eye closedBend for 1 – 1.5 seconds

Real application : Sham application = 2:1 (3 applications/spot), 2/3 = correctCorrect in every testing spot = Normal protective sensation

Hiatt, WR: Medical treatment of peripheral arterial disease and claudication. N Engl J Med 2001; 344:1608–21.

Consultation : Thyroid

Thyrotoxicosis

Thyrotoxicosis

Cardiovascular

• ↑ CHF, ↑ MI, ↑ arrhythmia

Gastrointestinal

• Hyperdefecation, ↑AST, ↑ ALT, ↑ ALP, ↑ GGT, Jaundice

Bone

• Bone loss, ↑ fracture, hypercalciuria, hypercalcemia

Reproductive

• Oligo/amenorrhea, gynecomastia in men

Hematologic

• Hypercoagulable state

Werner and Ingbar’s The Thyroid. 10th edition

Suspected Thyrotoxicosis

• Thyroid function test• If clinically equivocal : may consider screen TSH first

• Radioactive iodine uptake• Thyrotoxicosis without signs of Graves’ disease

• Suspected thyroiditis or thyrotoxicosis without hyperthyroidism (e.g. drug induced thyrotoxicosis)

• Thyroid scan• Thyrotoxicosis with palpable nodule(s)

• Thyroid ultrasound and color doppler ultrasound• Alternative to thyroid scan in thyrotoxicosis with nodule(s)

• Patents with indication for RAIU and thyroid scan, but cannot be exposed to radiation (e.g. pregnancy, lactating women)

ค าแนะน าส าหรบภาวะความผดปกตของตอมไทรอยด พ.ศ.2556

Thyroid Antibodies


• TSH receptor antibodies (TRAb)• High sensitivity and specificity for Graves’ disease

• Predicted Graves’ disease remission

• Predict risk of neonatal thyrotoxicosis

Graves’ Disease

Thyroid acropachy

• Digital clubbing

• Soft tissue swelling

• Periosteal new bone formation

Localized myxedema Exophthalmos

Thyroid bruit

Choice of Treatment

Adapted from 2016 ATA Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis

Situations Medical RAI Surgery

High likelihood of remission (eg. young age, small goiter, mild disease)

++ + +

Elderly with comorbidities ++ ++ X

Active GO ++ X ++

Large goiter + ++ ++

Suspected malignancy - X ++

Medication failure/toxicity - ++ ++

Toxic nodule(s) - ++ ++

Abbreviations: RAI: radioactive iodine, GO: Graves’ ophthalmopathy

Antithyroid Drugs

Characteristics Methimazole (MMI)

Propylthiouracil (PTU)

Half-life Longer (OD)Consider spilt to bid if dose > 20 mg/day

Shorter (bid or tid)

Effectiveness (at equivalence dose)

+++(MMI:PTU = 1:20)

++

Starting dose 10 – 30 mg/day 150 – 450 mg/day

Placental and lactation passage

Higher Lower

Inhibit peripheral conversion of T4 → T3

No Yes(dose > 600 mg/day)


Antithyroid Drugs

Characteristics Methimazole (MMI)

Propylthiouracil (PTU)

Half-life Longer (OD)Consider spilt to bid if dose > 20 mg/day

Shorter (bid or tid)

Effectiveness (at equivalence dose)

+++(MMI:PTU = 1:20)

++

Starting dose 10 – 30 mg/day 150 – 450 mg/day

Placental and lactation passage

Higher Lower

Inhibit peripheral conversion of T4 → T3

No Yes(dose > 600 mg/day)

MMI should be used as first line

Consider PTU in …

• First trimester of pregnancy

• Thyroid storm

• Minor reactions to MMI (rash, arthralgia)


Starting dose MMI 10 – 30 mg/day

Consider beta-blocker in all patients esp. elderly or thyrotoxic patient with resting HR > 90 bpm or existing CVD

F/U FT3,FT4 in 4 – 8 weeks, not TSH

Titrated down to a maintenance level (2.5-5 mg/day)

Maintain lowest possible dose for 12 – 18 months

Consider stop treatment if TSH normal

F/U TFT q 2 – 3 months

When euthyroidism is reached (FT3, FT4 normal)

Start monitor TSH after euthyroidism


Adverse Effects of Antithyroid

• Minor : Switch antithyroids + antihistamine

• Rash, urticaria, arthralgia, fever

• Major : Do not switch between antithyroids !

• Hepatotoxic, cholestasis

• Agranulocytosis

• Thrombocytopenia

• P-ANCA associated vasculitis

Monitoring

กอนเรมยาตานไทรอยด

• อาจพจารณาสง CBC, LFT

• ไมใหใชยากรณ ANC < 500, transaminase > 5 เทา

ระหวางการรกษาดวยยาตานไทรอยด

• สง CBC เฉพาะเมอมไขหรอเจบคอ

• สง LFT เมอมผนคน ตวตาเหลอง อจจาระซด ปสสาวะสเขม ปวดขอ แนนทอง คลนไสอาเจยน ออนเพลยมาก


Alternative Treatments

• Anti-thyroid drugs

• Inorganic iodine (SSKI, Lugol’s solution)

• Lithium

• Beta-blocker (i.e. propranolol > 160 mg/day)

• High dose glucocorticoid (Thyroid storm)

• Reduced enterohepatic recirculation of thyroid hormone

• Cholestyramine

• Remove thyroid hormone from circulation

• Peritoneal dialysis

• Plasmapheresis

• Definitive treatment

• Thyroidectomy / radioactive iodine ablation (RAI ablation)

Management Before-After RAI

• Euthyroidism or near-euthyroidism before RAI

• Beta-adrenergic blockade in patients at risk for complications

• Stop antithyroid 3-5 days before RAI

• Restart antithyroid after 3 – 7 days

• Birth control for 4 – 6 months in women and 3 -4 months

after RAI

• Considered 2nd dose if persistent thyrotoxicosis after 6 mo.

C. Sriphrapradang. Presented in RCPT annual meeting 2016.

Management Before-After Sx

• Euthyroidism before surgery

• Lugol’s solution 5 – 7 drops tid for 10 days before surgery (in

Graves’ disease)

• Stop MMI on operative day

• Beta blockers can be continued

• Monitor Ca, Alb after surgery

• Total thyroidectomy: Start LT4 1.6 μg/kg/day after surgery

Hypothyroidism

Hypothyroidism

Cardiovascular

• Dyslipidemia, CHF, pericardial effusion

Gastrointestinal

• Constipation, ileus, mild ↑AST, ALT (rare)

Musculoskeletal

• Myalgia, ↑ CK, rhabdomyolysis, carpal tunnel syndrome

Reproductive

• Menorrhagia

• Infertility

• Galactorrhea (↑PRL in 1o hypothyroid)


Hypothyroidism

Neurocognitive

• Poor memory, cognitive dysfunction

• Depression, psychosis

Kidney and electrolytes

• Decreased GFR

• Impaired free water clearance → Hyponatremia

Hematology

• Anemia (normocytic or macrocytic)

• Bleeding tendency

• Acquired vWD, impaired factor VIII activity


Suspected Hypothyroidism

• Thyroid function test

• FT4, TSH

• Not FT3

• Thyroid autoantibodies

• Anti-TPO, anti-Tg

• To diagnose Hashimoto’s thyroiditis


Thyroid Hormone Replacement

• Levothyroxine : 100 mcg/day or 1.6 mcg/kg/day

• Start lower dose if• Mild hypothyroidism

• Age > 50 years

• Pre-existing cardiovascular disease

• 30 – 60 min before meal or > 4 hours after meal

• Avoid taken with PPI, H2 blocker, Fe, Ca, coffee

• Monitor TSH, keep normal TSH

• F/U 4 – 8 weeks, if stable → 6 – 12 months


Subclinical Thyroid Disorders

Subclinical hyperthyroid Subclinical hypothyroid

Should treat• TSH < 0.1 and

• Age > 60 years• Osteoporosis• CVD, AF• High RAIU

Should treat• TSH > 10 and anti-TPO positive• Pregnancy or infertile

Consider treat• TSH 5 – 10 and

• Anti-TPO positive• Hypothyroid symptoms• CVD or CV risk factors e.g. DLP• Presence of goiter

Consider treat• TSH 0.1 – lower normal limit and

one of the above factors

After exclude other causes of high/low TSH

and repeat the testing within 8 weeks


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