HYPOTHYROIDISM Hypothyroidism By Elias S Hypothyroidism • A by nikeborome

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									Hypothyroidism
    By: Elias S.
           Hypothyroidism
• A common disorder associated with thyroid
  hormone deficiency resulting from a defect
  anywhere in the hypothalamic-pituitary-thyroid
  axis
   – Majority  primary thyroid D.
   – Less common TSH , TRH
• Prevalence
  – U.S. NHANES III on 17353 persons
               hypothyroidism… 4.6%
            (subclinical 4.3%, overt 0.3%)
• international
        2-5% ( to 15% by the age of 75)
• Autoimmune Hypothyroidism
    annual incidence: 4/1000 women, 1/1000 men
      Prevalence cont…….
• Age: … with age
  – More prevalent in elderly
  – Autoimmune hypoth.- Mean age at Dx- 60.
• sex: women >(5-8x) Men
      Framingham study in adults>60yrs
                 5.9%-women 2.4%- men
Race: more common-Japanese
 NHASESIII, U.S
 whites(5.1%)>Hispanic A.(4.1%)>African
 A(1.7%)
                 causes
• Worldwide:
  – iodine deficiency most common cause
• In areas of iodine sufficiency
   – Autoimmune thyroiditis (Hashimoto’s)
   – Iatrogenic causes
• Hypothyroidism
         - Primary H.
         - Central (secondary/tertiary)
• Primary hypothyroidism – 2 forms
    Subclinical       Overt( clinical)
  (TSH, N FT4,N FT3)    (TSH, FT4,FT3)
     Autoimmune hypothyroidism

• Ch. Autoimmune thyroiditis
                 (Hashimoto’s thyroiditis)
  – Caused by cell-and Ab mediatd destruction of
    thyroid tissue
  – Both humoral and cellular factors contribute
  – Cytotxic T cells
  – Auto Abs.. TPO 95%, Tg 60%,
               TSH-R bloking Ab 20%, TBII 10-20%
  Two forms Hashimoto’s(goitrous)thyroiditis
                 Atrophic thyroiditis
• Hashimotos              • Atrophic thyroiditis
(goitruos)thyroiditis
• Marked                  •  fibrosis
  lymph.infiltration      • Less lymph.
• Atrophy of thyroid        infiltration
 follicles with absence   • Thyroid follicles
  of colloid                completely absent
• Mild to moderate
  fibrosis                • Late stage of
                            Hashimotos thyroiditis
• Present with goiter     • Minimal residual
• Minimal or no Sx          thyroid tissue
                          • Overt symptoms
            Risk factors
• Genetic suseptibility
  – Polymorphism in: HLA DR3,-DR4,-DR5
  – CTLA-4(a T-cell regulating gene)
  –  in down’s S., Turners S.
• Env. Factors
  – High iodine intake
  – infection:
     congenital rubella s. - autoimmune H.
  – Cigarette smoking
         Iatrogenic causes
• Thyroidectomy
  – 1-4wks after total thyroidectomy
  – In the 1st yr in the majority of subtotal t.
      If euthyroid at one year, 0.5-1% chance of
    hypothyroidism each year
• Radioiodine(I-131)therapy
  • Months to yrs later
  • Dose dependant
• External neck/Total body irradiations
• Anti-thyroid drugs (over Rx of Hyperth.)
            Other causes
• Iodine deficiency
• Iodine excess (the wolf-chaikoff effect)
• Drugs – Ethanolamine, Lithium,
            Amiodarone, INF-alpha, IL2
  – In Hypothyroid P’ts taking T4:
  Chlestyramine,Iron salts - T4 absorption
  Rifampin, Phenytoin,Carbamazepin- clearance
  Amiodarone, glucocotricoids
                   - conversion of T4T3
       Other causes cont…
• Infiltrative diseases – rare
   – Fibrous thyroiditis(reidel’s
     th.),hemochromatosis,scleroderma,
      leukemia,amyloidosis
   – Infections: Tbc., P.carini
• Subacut thyroiditis                ESR
 (De-quervain’s,granulomatous) -ve TPOAB
• Silent(painless)thyroiditis –postpartum th.


           Normal ESR, +TPOAb
       Secondary/tertiary
     Hypothyroidism(Central)
• <1%
• TSH or TRH
  – Dx – inappropriatly low(low or N. TSH)
         low T4 and T3
• Causes
  • Hypopituitarism(tumor,surgery
    irradiation,sheehan’s s.,hypophysitis)
  • Mutations in TSH/TSH-R gene
  • Hypothalamic Damage
    (tumor,trauma,radiation,inf. D.)
  • Mutations in TRH-R gene
  • Drugs – Dopamine, lithium
• Dx - MRI
 Congenital hypothyroidism
• 1:4000 newborns
  • Thyroid g. agenesis 80-85%
  • Inborn errors of thyroid H. synthesis
                                  10-15%
  • TSH-R Ab mediated(Moinfant) 5%
  • Anti-thyroid (Moinfant)
• Majority – appear normal at birth
  • <10% - prolonged jaundice,feeding
    problem,hypotonia,enlarged tongue,delayed
    bone maturation, unblical H., cong.Malf.
• Permanent neurologeic D. – if Rx is
  delayed
Mechanisms          Symptoms               Signs
Slowing of          Fatigue, weakness      Slow mov’t, slow speech
                    Cold intolerance       Delayed relaxation of
Metabolic process   Dyspnea on                  tendon reflexes
                          exertion         Bradycardia
                    W’t gain               Carotenemia
                    Sleepiness
                    Cognitive
                        dysfunction
                    Mental retardation
                    Constipation
                    Growth failure
Accumulation of     Dry skin               Rough thick skin
                    Hoarsness of voice     Puffy face with
Matrix              Edema                    loss of eye brow
                                           Periorbital edema
                                           Enlargement of
                                                the tongue



others              Decreased hearing      HTN
                    Myalgia/ paresthesia   Pericardial/pleural
                    Proximal M. weakness           effusion
                    Depression             Ascitis
                    Menst. Irregularity    Galactorrhea
                    Infertility, Libido
                    Arthralgia
                    Pubertal delay
 Neurologic manifestations
• Mental state, poor concentration
• Poor memory , emotional lability
• Carpal tunnel S. (25-30%)
• Cerebellar ataxia (10-30%)
• Peripheral neuropathy
• Proximal muscle weakness
• Hashimoto’s encephalopathy
• Myxedema coma
   Metabolic Abnormalities
• Hyponatremia
• Hyperlipidemia (LDL, cholesterol)
• Hyperuricemia (Gout)
• serum creatinin
• carotenemia
•  drug clearance
          drug toxicity
                                    TSH


                 Elevated                       Normall

                                           Pituitary D.
                    FT4                    Supected?

   Normal                   Low            no               yes

     Mild               Primary     No further
                                                            FT4
hypothyroidism       hypothyroidism    test

         TPOAb-,
TPOAb+           TPOAb+               TPOAb-          low      Normal
          noSx
 or SX
                    Autoimmune   Rule out                   No further
                       Hypo.   Other causes                    test
          Annual                            Rule out drug effects,
T4 Rx    followup                            Sick euthyroid s.,
                            T4 Rx
                                          Then evaluate ant.pituit.f.
    disorders that affect TSH
• High TSH                   • Low TSH
  • 1° hypothyroidism          • 1° Hyperthyroidism
  • Non-thyroidal              • Incomplete recovery
    illness(5%)                   from Hyperthyroidism
  • Drugs:                     • Non-thyroidal illness
     Dopamin antagonists,                         (10%)
     Amiodarone,               • High HCG (early
    cholecystographic dyes       pregnancy, molar P.,
  • TSH-producing pit.               choriocarcinoma)
    Adenoma                    • Central hypothyroidism
  • Adrenal insufficiency      • Drugs:
  • Thyroid homone              Dopamin,
            resistance S.       Glucocorticoids
                                Somatostatin analogues
                                Phenytoin
      Other investigations
• CBC, ESR
• OFT, Electrolytes
• Lipid profile
• Uric acid
• FNA
Central hypothyroidism
  – Imaging studies(sellar/supracellar)
  – Other hormonal profiles (pituitary)
                Treatment
• Most P’ts …. Require lifelong Rx
• The Goals
     Restoration of euthyroid State
     Reversion of Sx &Sns
     Reduction of gotre
• Rx thyroid hormone replacement
   Synthetic thyroxin(T4)
   – A pro-hormone, 80% absorbed
   – Active hormone production controlled
      by the patient’s own physiologic Mech.
   – Long half-life(7days)
   – Once daily when steady state is reached
   – Should be taken in an empty stomach
        Replacement dose
• Adults <60 with out evidence of Heart D.
   1.6 mcg/kg/day (50-150)
• Older p’ts , p’ts with CHD
   1/2-1/4 of the dose(25-50mcg)
• P’t evaluation every 3-6wks
  • Measure T4(early phase), TSH
  • Dose adjustment by 12.5-25 ( or )
• Once steady state is reached
  • Maintenance dose, yearly evaluation with TSH
    Additional adjustment
• dose: Pregnancy
           Estrogen Rx
           Nephrotic syndrom
           coadministration of drugs
           that clearance orabsorbtion
• dose:    elderly
           marked w’t loss
           androgen therapy
            ?T3 ?T3+T4

• Not recommended
  – Wide fluctuations of serum T3 conc.
  – Multiple daily doses
  – Serum T4 remains low
• T3+T4 therapy
  – For some hypothyroid p’ts who remain
    symptomatic despite Rx + normal TSH
  – Meta-analysis of 11 trials  No benefit
    Central Hypothyroidism
• Think of other hormonal deficiencies
  – T4 Rx to p’ts with untreard 2° adrenal
    insuficiency acut adrenal crisis!
• Glucocorticoid with T4 Rx if adr. Insuff.
• Need less T4 than 1°hypothyroidism
• Rx monitoring by- FT4 (TSH – no value)

								
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