thyroid diseases. q1: the most common thyroid function disorder is? 1) graves’ disease 2)...
TRANSCRIPT
Thyroid Diseases
Q1: The most common thyroid function disorder is?
• 1) Graves’ disease• 2) Hypothyroidism• 3) Sub-acute thyroiditis• 4) Thyroid cancer
Q2: The most sensitive test for thyroid function is?
• 1) Free T4• 2) Free T3• 3) TSH• 4) Thyroid ultra sound
Q3: The best assay to confirm that a patient’s hypothyroidism is autoimmune in nature?• 1) Thyroid stimulating
immunoglobulins• 2) Anti-nuclear antibody• 3) TSH• 4) Thyroid peroxidase antibodies
Q4: The best assay to confirm that a patient’s hyperthyroidism is autoimmune in nature?• 1) Thyroid stimulating
immunoglobulins• 2) Anti-nuclear antibody• 3) TSH• 4) Thyroid peroxidase antibodies
Q5: Which is the best study to confirm the etiology of a patient’s thyrotoxicosis?
• 1) I123 thyroid scan/uptake• 2) Neck CT or MRI • 3) Thyroid ultrasound• 4) Fine needle aspiration of the
thyroid
Q6: Which is the best study to make the initial evaluation for thyroid nodules discovered on routine physical exam?
• 1) I123 thyroid scan/uptake• 2) Neck CT or MRI • 3) Thyroid ultrasound• 4) Fine needle aspiration of the
thyroid
Q7: Patient has a thyroid U/S showing a solid dominant (>10mm) nodule and normal thyroid function, what is your next step?
• 1) Re-check thyroid U/S in 1 year • 2) Fine needle aspiration of the
thyroid • 2) Neck CT or MRI • 4) I123 thyroid scan/uptake
Q8: Thyroid U/S shows homogeneous increased radiotracer uptake, the diagnosis is?• 1) Metastatic thyroid cancer• 2) Graves’ disease• 3) Toxic multi-nodular goiter• 4) Toxic thyroid nodule
Q9: Methimazole or propylthiouracil and used to treat hypothyroidism?
• 1) True• 2) False
Q10: Which is not an appropriate treatment for Graves’ disease?
• 1) Thyroidectomy• 2) Anti-thyroid medications such
as propylthiouracil or methimazole
• 3) Levothyroxine sodium • 4) I131 radioactive iodine
Follicular cells arranged in clumps. Clumps of cells contain colloid. Colloid an iodine containing protein
called thryoglobulin. This is the precursor and storage form of thyroid hormone.
Thyroxine (T4), Triiodothyronone (T3)
Synthesis and Secretion
T4 and T3 circulate in the blood bound to plasma proteins.
TBG(70%), TBPA(20%) and albumin(10%).
T3 is the active form, 5 times more active than T4.
T4 is converted to T3 outside the thyroid, mostly in liver and kidney.
T3 binds to a nuclear receptor
Thyroid hormone action
T4 and T3 circulate in the blood bound to plasma proteins.
TBG(70%), TBPA(20%) and albumin(10%).
T3 is the active form, 5 times more active than T4.
T4 is converted to T3 outside the thyroid, mostly in liver and kidney.
T3 binds to a nuclear receptor
Thyroid hormone action
TRH secreted from hypothalmus controls TSH production.
TSH from anterior pituitary stimulates secretion of T4 and T3 from thyroid.
Regulated by a negative feedback loop.
Regulation of the H-P-T axis
Major Thyroid Abnormalities
Functional / Biochemical• Hypothyroidism• Hyperthyroidism
Structural / Anatomy
• Thyroid– Goiter
– Nodules• Cold• Warm or Hot
– Cysts– Malignancies
At Risk Population for Thyroid Dysfunction
• Women, elderly, postpartum 4-8 months.• FamHx of Hashimoto’s or Graves’ dz.• PMHx or FamHX autoimmune diseases –
SLE, RA, DM1, Addison’s, vitiligo, pernicious anemia.
• Type 1 DM: ~20% increase risk for thyroid dysfunction, mainly hypothyroid.
• Patients treated with amiodarone, lithium, others
HYPOTHALAMIC / PITUITARY THYROID AXIS
• TRH: stimulate anterior pituitary to release TSH.
• TSH: stimulate thyroid for synthesis and release of T4 and T3.
• Low T4, Low T3: stimulate TSH and TRH.
• High T4, High T3: inhibit TSH and TRH.
THYROID HORMONES
• T4 to T3 secretion ratio of 10:1.• T3 is 4X more biologically active than
T4.• T1/2: T4 = 7days, T3 = 1 day.• T4,T3: 99% bound to protein, i.e.
metabolically inactive.• From thyroid: 100% - T4, 20% - T3
remainder of T3 is from T4 to T3 conversion in peripheral tissues.
THYROID TESTINGBiochemical
TSH - highly sensitive, best test for thyroid function.
1) Free T4 (FT4)- biologically active.
2) Free T3 (FT3) - biologically active.
- rarely need to check unless, TSH is low or undetectable with a normal FT4.
THYROID TESTING(more specific)
• Thyroid Peroxidase Antibodies (TPO-Ab’s) - Hashimotos Thyroiditis• Thyroid Stimulating Immunoglobulins (TSI’s)
or TSH receptor antibodies (TRAb). - Unique to Graves’ disease• I-123 RAIU (Radio Active Iodine Uptake)
evaluation for thyrotoxicosis, shape, size. Don’t use to confirm hypothyroidism.
DON’T FORGET THE BASICS
• History of present illness and ROS.• PMHx – postpartum
– Past Hx of thyroid pain/tenderness/nodule/ enlargement or goiter
– H/O autoimmune diseases• FamHX – thyroid dysfunction, thyroid
cancer, Autoimmune diseases.• Medications• Systematic physical exam
Hypothyroidism
HYPOTHYROIDISM
• Prevalence: 4 - 8% general population.
• Mean age of Dx: 5th decade of life• Female to male ratio: 10:1
Hypothalamic disease Pituitary disease
Secondary hypothyroidism-causes
PRIMARY HYPOTHYROIDISM
• Identification on clinical basis can be challenging.
• Symptoms generally vague.• Frequently goes unnoticed, confused as
other health problems.• Insidious onset + poor index of
suspicion = misdiagnosis
ETIOLOGY
• Autoimmune:
- Chronic lymphocytic thyroiditis = Hashimoto’s
- positive TPO-Ab’s
- remember postpartum thyroiditis • Iatrogenic: I-131 RAI, total/subtotal
thyroidectomy, neck irradiation.• Congenital: agenesis, dysgenesis.• Drug induced: lithium, amiodarone,
chemotherapy, others.
Clinical Symptoms of Hypothyroidism
• Fatigue• Lethargy• Cold intolerance • Constipation• Decreased
memory• Depression• Mental
Impairment
• Arthralgias • Hoarseness• Heavy menstrual
flow• Paresthesias• Sleepiness• Weight
gain ,edema• Muscle cramps
Clinical Signs of Hypothyroidism
• Bradycardia• Coarse hair, hair loss• Delayed relaxation phase of deep tendon reflexes• Dry, cool, pale skin• Goiter• Hoarseness• Non-pitting edema (myxedema)• Puffy eyes and face• Slow movements• Slow speech• Thinning lateral third of eyebrows
Example of Clinical Manifestationsof Hypothyroidism
• Patient example– Fatigue (“no energy”), cold
intolerance, constipation, weight gain, fatigue, problems with concentration (“mental clouding”), dry skin
CLINICAL MANIFESTATONSEXAM
• NECK: thyroid may be normal, enlarged, symmetric/asymm., smooth or lumpy.
• HEART: bradycardia.• EXTREMS: pretibial/ankle edema, dry
cool skin, brittle nails.• NEURO: DTR’s with delayed relaxation
phases• HEENT: periorbital puffiness, loss of
lateral eyebrows, coarse/thinning hair.
Dry skin Erythema ab igne Vitiligo
Infertility Menorrhagia Galactorrhoea
Clinical FeaturesSkin and Reproduction
Aches and Pains Carpal Tunnel Deafness Hoarseness Ataxia Depression Psychosis
Iron deficiency A Pernicious Anemia
Clinical FeaturesNeurological and Haematological
LABORATORY EVALUATION
• TSH - high • Free T4 - low• Check both if new diagnosis to make
sure PITUITARY-THYROID AXIS intact.
• Consider TPO-Ab
Fasting cholesterol and triglycerides may be raised
Ck AST and LDH (SMAC 20) may be raised
FBC Anemia ECG Slow rate. Small complexes.
Additional abnormal tests.
Levothyroxine Sodium (LT4 )
• Exogenously administered LT4 hormone• Indistinguishable from endogenous T4,
both in its physiologic effects and its quantification as measured in blood
• LT4 is the treatment of choice as replacement or supplemental hormone therapy
• Branded preparations are preferred
TREATMENT • Levothyroxine (LT4), narrow
therapeutic range– 0.3 – 3.0 IU/mL, caution
in lower range TSH.• Brand vs. generic vs. T4 + T3
combination.• Lifelong treatment, most
cases• Dosing: 1.6 mcg/kg/day =
~100 - 125 mcg/day.• Compliance, empty stomach,
competing agents for absorption (Iron, Calcium )
• Check TSH no sooner than 6 weeks after initial start of LT4 or any adjustment.
Therapy Monitoring
• Clinical and laboratory monitoring enable– Evaluation of the clinical response– Assessment of patient compliance– Assessment of drug interactions, if applicable– Adjustment of dosage, as needed
• Clinical and laboratory evaluations should be performed – At 6- to 8-week intervals while titrating– Annually once a euthyroid state is established
Factors That May Reduce Levothyroxine Effectiveness• Malabsorption Syndromes
– Post jejunoileal bypass surgery
– Short bowel syndrome– Celiac disease
• Reduced Absorption– Colestipol
hydrochloride – Sucralfate– Ferrous sulfate– Food (eg, soybean
formula)– Aluminum hydroxide– Cholestyramine– Sodium polystyrene
sulfonate
• Drugs That Increase Clearance– Rifampin– Carbamazepine– Phenytoin
• Factors That Reduced T4 to T3 Clearance– Amiodarone– Selenium deficiency
• Other Mechanisms– Lovastatin– Sertraline
Thyroid Hormone TherapySpecial Treatment Populations
• Patients 50 years of age or with underlying cardiac disease– Initial dose of LT4 - 25 to 50 mcg/d
• Elderly patients with cardiac disease– Initial dose of LT4 - 12.5 to 25 mcg/d
• Patients with heart failure– Both hypo- and hyperthyroidism can
worsen heart failure
Treating Hypothyroidism Before and During Pregnancy
• Encourage adherence with LT4 replacement therapy before conception
• Monitor TSH levels before conception and during first trimester
• Consider increase of LT4 dosage in athyreotic patients by 25% - 50% when pregnancy is confirmed
• Monitor TSH levels every 6 to 8 weeks throughout pregnancy
• Reinstate pre-pregnancy LT4 dosage immediately following delivery
Over-Replacement Risks
• Switching a narrow therapeutic index drug, such as LT4, without retesting and re-titrating can cause inconsistent TSH control, resulting in over-replacement
• Over-replacement risks (TSH <0.5 IU/mL)
– Iatrogenic thyrotoxic state– Increased heart rate and myocardial contractility– For cardiac patients, increased risk of angina and MI– Reduced bone density/osteoporosis– Psychiatric symptoms, such as anxiety, sleep
disturbance, irritability, and fatigue
Case 1
46 y.o. female presents with a 3 - 4 month history of heavier than usual menstrual cycles, fatigue, “feeling sleepy all of the time”, depressed, constipation, problems concentrating, cold intolerance.
• PMHx: unremarkeable• FAMHx: Adopted.
Case 1 continued
• P.E. : DTR’s show delayed relaxation phases of biceps and brachioradialis, non tender symmetric goiter @ 2 times normal size without nodules.
• LABS : TSH 77.02 (0.45-4.50) Free T4 0.38 (0.8 – 1.50)
TPO-Ab 267 reactive greater 40.
Case 1 continued
• Dx: Hashimoto’s Thyroiditis• Tx: 100 mcg qd, non-generic LT-4 Follow-up in 6 weeks and recheck TSH• F/U: Feeling “90% better”
TSH 7.62 Increase to 112mcg qd. Follow-up in 2 months.
• 2 months later TSH – 2.11 (0.50 - 3.00). Plan: follow and adjust LT-4 based on TSH
SUBCLINICAL HYPOTHYROIDISM
• Very difficult to diagnose clinically• High index of suspicion, may be asymptomatic• 4 -15% of general population*• 20% of pts. over 60 y.o. (esp. women)**• LABS: TSH - minimally high (6 - 10 IU/mL) Free T4 – low normal• TREATMENT: controversial, consider if
symptoms, lipid abnormality, if TPO-Ab positive
• Low dose LT-4 vs. surveillance, education.
Mild Thyroid Failure and Neurobehavioral Abnormalities
• Conditions reported to occur more frequently in patients with mild thyroid failure – Depression– Anxiety– Somatic complaints– Cognitive abnormalities
Rationale for Treating Mild Thyroid Failure
• Potential benefits from treatment– Prevent progression to overt
hypothyroidism– Improve serum lipid profile, which
may reduce the risk of death from cardiovascular causes
– Reduce symptoms, including psychiatric and cognitive abnormalities
Repeat tests after an interval. If TSH is continuing to rise in the presence
of strongly positive antibodies, the risk of developing hypothyroidism in the future is high. Thus treatment with thyroxine at this early stage may be justified if symptomatic.
Beware-Thyroxine may not cure all symptoms.
Treatment
Case 2
• Hx: 32 y.o. women referred for mildly increased TSH 8.69 (0.46-4.68)
• Symtoms: mild fatigue, dry skin, “not feeling my usual self”
• PMHx: no H/O thyroid disorders, or recent of remote thyroid pain/tender.
• FAMHx: Mother, two maternal aunts with hyperthyroidism.
Case 2 continued
• P.E. : Thyroid minimally enlarged and non-tender, no nodules. remainder of exam unremarkable.
• Labs: TSH 7.5 (.46 – 4.68)
FREE T4 0.82 (0.80-1.50). TPO-Ab 317 reactive greater than 40
Case 2 continued
• DX: Subclinical Hypothyroidism• Hashimotos thyroiditis
• Tx: “Brand LT4” 25 mcg q.d. Follow-up and TSH in 2 months.• Follow-up: patient feeling better
without complaints TSH 1.89 (0.5 – 3.0) Education, need to follow
Non specific symptoms Osteoporosis Anemia Heart Failure Treatment with thyroxine Start with small doses and titrate
slowly. (25ug).
Elderly
Incidence is about 9%. Transitory or permanent. Early hyperthyroidism (<4/12), later
hypothyroidism (>4/12), euthyroid 10/12 later.
Increased microsomal antibodies. Thyroxine
Post-partum thyroiditis.
Requires prompt treatment. Mortality of 50%.
Suspect in cases of hypothermia. T3 20ug bd IM Steroids recommended Glucose to correct hypoglycaemia Rewarming Assisted ventilation
Myxoedema Coma
Hyperthyroidism
HYPERTHYROIDISMETIOLOGY
• Graves’ disease ( autoimmune ).• Toxic multi-nodular goiter ( toxic MNG ).• Toxic nodule (hot or warm nodule)
Common Symptoms and Signs of Thyrotoxicosis
Symptoms
• Nervous / shaky
• Fatigue• Muscle weakness• Increased perspiration
• Heat intolerance• Tremor• Palpitations• Appetite/weight changes Menstrual disturbances
Signs
• Goiter • Hyperactivity • Tachycardia /
arrhythmia • Systolic hypertension• Warm, moist, or smooth
skin• Stare and eyelid
retraction• Tremor • Hyper-reflexia
GRAVES’ Dz
• ~75% of cases of hyperthyroidism.• Thyroid Stimulating Immunoglobulins (TSI’s)
and / or TSH receptor antibodies (TRAb) levels usually increased
• Incidence 2nd – 4th decade of life.• ~5 times more likely in women.
Thyrotoxicosis - work-up
• Labs- demonstrate thyrotoxicosis.– TSH - Low or undetectable – Free T4 and/or Free T3 – Increased
I123 thyroid scan / uptake• Uptake is increased.
– 4 hour: normal ref. (5 – 15%)– 24 hour: normal ref. (6 - 30%)
• Scan (anatomical findings via radiotracer uptake)– Homogeneous ( Graves’ Dz)– multiple areas (Toxic MNG)– single area (Hot or warm nodule)
PATIENT EXAMPLEGRAVES’
• 30 y.o. female with nervousness, shakiness, heat intolerance, “fast / pounding heart beat”, wt loss, light menses, and muscle weakness for 3 months.
• P.E. HR=118– Eyes—lid lag, stare,
– Skin: warm/moist– Thyroid: large symmetric non-
tender gland– Neuro—tremors, DTR’s – brisk,
hyper-reflexic • LABS: TSH: < 0.03 (0.45 – 4.50)
FT4: 2.8 (0.8-1.8)
Graves’ Work up Cont.
• I123 thyroid S/U 4hr = 28% (5 - 15%) 24hr = 76% (6 - 30%) diffuse homogeneous uptake.
TREATMENT options
Treatment of Hyperthyroidism
Treatment depends upon -Cause and severity of disease -Patients age -Goiter size -Comorbid condition -Treatment desired
Treatment
The goal of therapy is to correct hyper-metabaolic
state with fewest side effects and lowest incidence of hypothyroidism.
Options Anti-thyroid drugs Radioactive iodine Surgery Beta-blocker and iodides are adjuncts to above
treatment
Beta Blockers
Prompt relief of adrenergic symptoms Propranolol widely used Any beta blocker can be used, but non-
selectives have more direct effect on hyper-metabolism
Start with 10-20 mg q6h Increase progressively until symptoms are
controlled Most cases 80-320 mg qd is sufficient CCB can be used if beta blocker not tolerated
or contraindicated
Iodides
Iodide blocks peripheral conversion of T4 to T3 and inhibits hormone release. These are used as adjunct therapy
• Before emergency non-thyroid surgery• Beta blockers cannot curtail symptoms• Decrease vascularity before surgery for
Grave’s disease
Iodides
Iodides are not used for routine treatment because of paradoxical increase of hormone release with prolonged use
Commonly used: Radiograph contrast agents -Iopanoic acid -Ipodate sodium Potassium iodide Dose 1 gram/ 12 weeks
Anti-thyroid Drugs
They interfere with organification of iodine—suppress thyroid hormone levels
Two agents: -Tapazole (methimazole) -PTU (propylthiauracil)
Anti-thyroid Drugs
Remission rate: 60% when therapy continued for two years
Relapse in 50% of cases. Relapse more common in -smokers -elevated TS antibodies at end of therapy
Anti-thyroid Drugs
Methimazole
Drug of choice for non-pregnant patients because of :
Low cost Long half life Lower incidence of side effects Can be given in conjunction with beta-blocker Beta-blockers can be tapered off after 4-8
weeks of therapyDose 15-30 mg/day
Anti-thyroid Drugs
Methimazole Monthly Free T4 or T3 until euthyroid Maintenance dose 5-10 mg/day TSH levels may remain undetectable for months
after euthyroid and not to be used to monitor the therapy
Anti-thyroid Drugs
Methimazole At one year if patient is clinically and
biochemically euthyroid and TS antibodies are not detectable, therapy can be discontinued
Monitor every three months for first year then annually
Relapses are more common in the first year but can occur years later
If relapse occurs, iodide or surgery although anti-thyroid drugs can be restarted
Anti-thyroid Drugs
PTU Prefered for pregnant patients Methimazole is associated with rare genetic
abnormalities Dose 100 mg t.i.d Maintenance 100-200 mg/day Goal: Keep Free T4 at upper level of normal
Anti-thyroid Drugs
Complications Agranulocytosis up to 0.5% High with PTU Can occur suddenly Mostly reversible with supportive Tx Routine WBC monitoring controversial Some people monitor WBC every two weeks
for first month then monthly Advised to stop drug if they develop sudden
fever or sore throat
Treatment with 1131 RAI
• Treatment of choice– Goal is complete ablation i.e. hypothyroid– Hypothyroid about 3-5 months post I131 Tx
• Follow Free T4 q 4-6 weeks until low– Treatment: “brand” LT4– Follow and treat as you would for hypothyroid– Exception: the low TSH usually lags behind,
often for months, the normalization of the Free T4.
– Check Free T4 and TSH until the TSH becomes normal or high, then only follow the TSH.
Thyroid Nodules
How thyroid nodules or masses are found?
• By HCP: palpation on routine exam• By patient: rarely• Incidentally
– CT scan or MRI of chest / neck – Carotid Dopplers
• Thyroid Ultrasound• I123 thyroid scan / uptake
Thyroid Nodules
• 5 categories: – Benign– Non-diagnostic– Follicular neoplasm/lesion– Suspicious– Malignant.
• Size - >1cm “dominant nodule”
Thyroid Nodules
• I123 thyroid scan / uptake – Hot or warm – hormone secreting
nodules– Cold nodules can be:
• Cysts• Benign adenomas• Malignant tumors• others
Ultrasound findings that increase the risk of malignancy
• Hypoechoic• Microcalcifications• Irregular margins• Intranodular vascularity• Rounded appearance; more tall than
wide, shape of the nodule
Suspicious for malignancy
• Growing nodule• Fixed nodule• Firm or hard consistency• Cervical adenopathy• History of head and neck irradiation• Family history of medullary thyroid carcinoma
(MTC), multiple endocrine neoplasia type 2 (MEN 2), or papillary thyroid carcinoma (PTC)
• Persistent dysphonia, dysphagia or dyspnea• Age <30 or >60 years• Male sex
Thyroid Nodule Work-up
• Assess for biochemical abnormality. (TSH, FT4, ?FT3)
• If normal Labs – U/S to evaluate: number and echotexture.– Cytopathological Eval. Fine needle aspiration (FNA)
with or without U/S guidance.• If abnormal Labs:
low TSH and or increased FT4/FT3 – I123 thyroid scan and uptake– Nodule(s) hot or warm– Treat options: I131 RAI, ATD’s, Surgery, refer to
endocrinologist for treatment
Cold Nodules on I123 Thyroid scan/uptake
• TSH and Free T4 normal– Consider thyroid cancer, benign adenoma,
or thyroid cyst– Ultrasound to delineate solid vs. cystic
lesion– Referral for ultrasound guided FNA biopsy– If biopsy is suspicious for cancer or
demonstrates cancer, referral to surgeon with ample experience in thyroid surgery.
Thyroid Malignancies
• Papillary: ~80%• Follicular: ~15%• Medullary: ~3-5%• Anaplastic: < 2%