Download Thyrotoxicosis Mita Sanghavi Goel, M.D. December 11, 2002

THYROTOXICOSIS
Mita Sanghavi Goel, M.D.
December 11, 2002
Overview
Thyrotoxicosis is a syndrome of illnesses that result from tissues being exposed to, and responding to excess thyroid
hormone. This may result from any cause that disrupts the physiology of thyroid hormone synthesis or regulation.
Physiology
Synthesis
• Thyroid hormone (T3 and T4) is made by the following process
 Iodide is actively taken up by the follicular cells of the thyroid and enters the lumen of the follicle
 Iodide is oxidated (with the help of thyroid peroxidase)
 Tyrosyl residues of thyroglobulin are iodinated with this oxidated iodide, forming mono- and diiodotyrosine
 Iodotyrosinases are coupled to form biologically active thyronines (T3 and T4) with the help of thyroid
peroxidase
Regulation
• TRH secreted by the median eminence of the hypothalamus stimulates TSH secretion
• TSH secreted by the anterior pituitary stimulates secretion thyroid hormone from the thyroid (mostly T4)
• T4 is converted in peripheral tissues to the more potent T3
• Negative feedback to the pituitary occurs largely via free T3 and free T4.
Causes of thyrotoxicosis
Associated with hyperfunctioning thyroid
• Excess production of TSH
• Abnormal stimulation of thyroid: Graves’ disease, trophoblastic tumor
• Intrinsic thyroid autonomy: hyperfunctioning adenoma, toxic multinodular goiter
Not associated with hyperfunctioning thyroid
• Disorders of thyroid storage: subacute thyroiditis
• Extrathyroid source of hormone: thyrotoxicosis factitia, “hamburger toxicosis”, ectopic thyroid tissue (struma
ovarii)
Manifestations
General thyrotoxicosis
• Skin and Hair
 Warm, moist skin that results from cutaneous vasodilation and excessive sweating
 Fine, friable hair occasionally with excessive hair loss.
 Onycholysis, vitiligo, alopecia areata
• Pulmonary
 Increased oxygen consumption and CO2 production
 Respiratory muscle weakness can cause fatigue and dyspnea
• Ocular
 Retraction of the upper eyelid (presence of rim of sclera between the lid and the limbus)
 Lid lag
• Cardiovascular
 Supraventricular tachycardias such as atrial fibrillation (10% of patients with thyrotoxicosis)
 Increased cardiac output because of increased
stroke volume and increased heart rate (via
direct inotropic effect of thyroid hormone) 
may lead to chf in patients with underlying
heart disease.
 Increased circulatory demands can cause
secondary increase in cardiac output.
 Widened pulse pressure from increasing
systolic and decreasing diastolic pressure.
 Low SVR
 Low total and HDL cholesterol
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•
Gastrointestinal
 Increased frequency of bowel movements, but rarely diarrhea
 Occasionally increased appetite with weight loss
 Abnormal LFTs may result, especially elevated alk phos
• Neurologic
 May reflect increased adrenergic activity
 Hyperactive DTRs, tremulousness
 Nervousness, emotional lability, hyperkinesia
• Musculoskeletal
 Proximal muscle weakness with no fasciculation on exam or inflammatory changes on biopsy
 Increased excretion of calcium and phosphorus in urine and stool leading to demineralization of bone
(cortical>trabecular)
• Hematologic
 Red blood cells are normal, but the red blood cell mass is increased.
 Plasma volume also increases, resulting in a normocytic, normochromic anemia.
Graves’ Disease
• Diffuse goiter: may be asymmetric, but generally diffusely enlarged, soft, and vascular (occ. with a bruit).
• Ophthalmopathy: in addition to the findings mentioned above, patients may develop exophthalmos of varying
degrees with ophthalmoplegia and congestive oculopathy secondary to inflammatory infiltrate with lymphocytes,
mast cells, and plasma cells.
• Dermopathy: thickening of the dermis with infiltration by lymphocytes. Presents as a raised, hyperpigmented,
violaceous papular rash, often over the shins.
Diagnosis
Bloodwork
TSH, Free T3, Free T4
Thyroid-receptor antibodies
Not required for the diagnosis of Graves disease if physical exam suggestive of Graves’
Imaging
Radioactive Iodine Uptake
High Uptake: Graves’, toxic multinodular goiter,
Low Uptake: thyroid hormone ingestion, thyroiditis
Treatment
Symptomatic
Beta-blockers: Diminish the symptoms caused by increased beta-adrenergic tone, such as palpitations,
tachycardia, tremulousness, anxiety, heat intolerance, and congestive heart failure.
Antithyroid
Thionamides
 Propylthiouracil (PTU): Blocks the oxidation of iodine and iodination of thyroglobulin. Safe in pregnancy
 Methimazole: Similar to PTU, but blocks peripheral conversion of T4 to T3. Lower risk of agranulocytosis.
Iodinated contrasts and iodine
 Potent inhibitors of peripheral conversion of T4 to T3
 May cause resistant hyperthyroidism; therefore, not used alone.
Other oral agents
 Glucocorticoids block peripheral conversion of T4 to T3 and, in Graves’, reduce thyroid secretion
 Lithium blocks thyroid hormone release
 Cholestyramine combined with methimazole lowers T4 and T3 concentrations faster than methimazole alone
 Carnitine is a peripheral antagonist of thyroid hormone and is being investigated for clinical use
Ablative
Radioactive
 Administered at sodium 131I, radioiodine produces ablation in 6-18 weeks, but may only be attempted after
control of severe hyperthyroidism or establishment of only mild hyperthyroidism
 Should be done 6 months in advance for any woman planning pregnancy to avoid need for thinoamides.
Surgical
 Generally only indicated if evidence of obstruction from the goiter or otherwise intolerant of other therapies
Preventive/Follow Up
1200-1500 mg of calcium daily to prevent reduced bone density and increased fracture risk.
Assess thyroid function at 4-6 week intervals until achievement of stable therapy.
Beth Israel Deaconess Medical Center Residents’ Report