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Toronto Notes 2019 Thyroid Hypothyroidism
Definition
• clinicalsyndromecausedbycellularresponsestoinsufficientthyroidhormoneproduction
Epidemiology
• 2-3%ofgeneralpopulation
• F:M=10:1
• 10-20%ofwomen>50havesubclinicalhypothyroidism(normalT4,TSHmildlyelevated) • iodinedeficiencymostcommoncauseworldwide,butnotinNorthAmerica
Etiology and Pathophysiology
• primaryhypothyroidism(90%)
■ inadequate thyroid hormone production secondary to intrinsic thyroid defect
■ iatrogenic: post-ablative (I-131 or surgical thyroidectomy)
■ autoimmune: Hashimoto’s thyroiditis, chronic thyroiditis, idiopathic, burnt out Graves’ ■ hypothyroid phase of subacute thyroiditis
■ drugs: goitrogens (iodine), PTU, MMI, lithium
■ infiltrative disease (progressive systemic sclerosis, amyloid)
■ iodine deficiency
■ congenital (1/4,000 births)
■ neoplasia
Endocrinology E27
Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review
Clin Ther 2017;39(2):378-403
• GIdisorderssuchasceliacdisease,atrophicgastritis,
lactose intolerance, H.pylori infection may impede
levothyroxine absorption.
• Drugsdecreasingstomachacidityhavebeenshown
to significantly reduce exogenous thyroid hormone absorption from the GI tract. These include: proton- pump inhibitors, H2 receptor antagonists, calcium carbonate, sucralfate and aluminum hydroxide.
• Ironcitrateisshowntoreduceintestinalabsorptionof levothyroxine.
• Food,especiallysoybeansandcoffee,havebeenshown to reduce absorption of levothyroxine significantly.
• Roughly 80% of levothyroxine is absorbed within 3
hours after administration of the drug. Thus, patients should be educated to take levothyroxine on empty stomach at least one hour prior to eating breakfast.
Thyroid Hormone Replacement for Subclinical Hypothyroidism
Cochrane DB Syst Rev 2007;3:CD003419
Purpose: To assess the effects of thyroid hormone replacement for subclinical hypothyroidism.
Study Selection: RCTs comparing thyroid hormone replacement with placebo in adults with subclinical hypothyroidism. Minimum duration of follow-up was one month.
Results: No trial assessed (cardiovascular) mortality or morbidity. Seven studies evaluated symptoms, mood, and quality of life with no statistically significant improvement. One study showed a statistically significant improvement in cognitive function. Six studies assessed serum lipids; there was a trend for reduction in some parameters following levothyroxine replacement. Some echocardiographic parameters improved after levothyroxine replacement therapy, like myocardial relaxation. Only four studies reported adverse events with no statistically significant differences between groups.
Conclusions: In current RCTs, levothyroxine replacement therapy for subclinical hypothyroidism did not result in improved survival or decreased cardiovascular morbidity. Data on health-related quality of life and symptoms did not demonstrate significant differences between intervention groups. Some evidence indicates that levothyroxine replacement improves some parameters of lipid profiles and left ventricular function.
Signs and Symptoms of Hypothyroidism HIS FIRM CAP
Hypoventilation Intolerance to cold Slow HR
Fatigue Impotence
Renal impairment Menorrhagia/amenorrhea Constipation
Anemia
Paresthesia
• secondary hypothyroidism: pituitary hypothyroidism ■ insufficiency of pituitary TSH
• tertiary hypothyroidism: hypothalamic hypothyroidism ■ decreasedTRHfromhypothalamus(rare)
• peripheraltissueresistancetothyroidhormone(Refetoffsyndrome)
Table 20. Interpretation of Serum TSH and Free T4 in Hypothyroidism
Overt Primary Hypothyroidism Subclinical Primary Hypothyroidism Secondary Hypothyroidism
Clinical Features
Serum TSH
Increased
Increased
Decreased or not appropriately elevated
Free T4
Decreased Normal Decreased
Table 21. Clinical Features of Hypothyroidism
Fatigue, cold intolerance, slowing of mental and physical performance, hoarseness, macroglossia
Pericardial effusion, bradycardia, hypotension, worsening CHF + angina, hypercholesterolemia, hyperhomocysteinemia, myxedema heart
Decreased exercise capacity, hypoventilation secondary to weak muscles, decreased pulmonary responses to hypoxia, sleep apnea due to macroglossia
Weight gain despite poor appetite, constipation
Paresthesia, slow speech, muscle cramps, delay in relaxation phase of deep tendon reflexes (“hung reflexes”), carpal tunnel syndrome, asymptomatic increase in CK, seizures
Menorrhagia, amenorrhea, impotence
Puffiness of face, periorbital edema, cool and pale, dry and rough skin, hair dry and coarse, eyebrows thinned (lateral 1/3), discolouration (carotenemia)
Anemia: 10% pernicious due to presence of anti-parietal cell antibodies with Hashimoto’s thyroiditis
• L-thyroxine(doserange:0.05-0.2mgPOOD~1.6μg/kg/d)
• elderlypatientsandthosewithCAD:startat0.025mgdailyandincreasegraduallyevery6wk(start
low, go slow)
• afterinitiatingL-thyroxine,TSHneedstobeevaluatedin6wk;doseisadjusteduntilTSHreturnsto
normal reference range
• oncemaintenancedoseachieved,follow-upTSHwithpatientannually
• secondary/tertiaryhypothyroidism
■ monitor via measurement of free T4 (TSH is unreliable in this setting)
CONGENITAL HYPOTHYROIDISM
• seePediatrics,P28
General CVS
Respiratory
GI Neurology
GU Dermatology
Hematology
Treatment