Medical Pharmacology Chapter 30:  Thyroid and Antithyroid Drugs

Thyrotoxicosis

• Definition:  clinical, physiological, biochemical consequences when tissues respond to excess thyroid hormone

• Most important causes: those associated with prolonged hormone overproduction by the thyroid.

• Causes

  • Extra-pituitary unregulated thyroid stimulation:

    1. Graves' disease

    2. Hashimoto's disease

    3. trophoblastic tumor

  • Chronic thyroiditis

  • Excessive TSH secretion by pituitary tumor (rare)

  • Autonomous thyroid gland hyperfunction

  • Ingestion of meat contaminated with animal thyroids ("hamburger toxicosis")

• Hyperthyroidism is only associated with conditions in which thyroidal hyperfunction leads to thyrotoxicosis.

Graves' disease

• Three major presentations

  • Hyperthyroidism with diffuse goiter

  • Dermopathy

  • Ophthalmopathy

• Thyroid Pathology

  • Soft, enlarged, vascular

  • Parenchymal hypertrophy/hyperplasia

  • Lymphocytic infiltration (suggesting the immunological nature of the disease)

    •  

      "Diffuse toxic goiter of Graves disease"

      "Diffuse toxic goiter of Graves disease, gross, showing symmetric, non-nodular hypervascular enlargement of the thyroid" ©1999 KUMC Pathology and the University of Kansas, used with permission; courtesy of Dr. James Fishback, Department of Pathology, University of Kansas Medical Center.

• Graves' disease: other involvements

  • Generalized lymphoid hyperplasia and infiltration

  • Spleenic or thymic enlargement

  • Thyrotoxicosis associated with:

    • Skeletal muscle fiber degeneration

    • Cardiac enlargement

    • Diffuse liver fibrosis with fatty infiltration

    • Skeletal decalcification

    • Body tissue loss

• Ophthalmopathy:  characterized by:

  1. Inflammatory orbital content infiltrate (lymphocytes, mast cells, plasma cells)

  2. Enlargement of orbital musculature (lymphocytes infiltration, mucopolysaccharides, edema, fat)

  3. Eventually muscle fiber degeneration; loss of striations; fibrosis

• Dermopathy

  • Dermal thickening (lymphocytes infiltration; mucopolysaccharides)

• Clinical Presentations of Thyrotoxicosis

  • Common manifestations (thyrotoxicosis)

    • Nervousness, insomnia, tremors, frequent bowel movements, heat intolerance, sweating, emotional instability

    • Weight loss despite adequate or increased appetite

    • Muscle weakness

    • Oligomenorrhea/amenorrhea in premenstrual women

    • Dyspnea

    • Palpitations

    • Exacerbation of angina/cardiac failure (older patients)

  • Ocular Presentations: (distinct from ophthalmopathy associated with Graves' disease)

    • Ocular signs mainly due to excessive sympathetic stimulation

      • Characteristics stare (widening palprebral fissures)

      • Lid lag

      • Infrequent blinking

      • Failure to wrinkle brow upon upward gaze

  • Cardiovascular effects

    • Wide pulse pressure

    • Sinus tachycardia

    • Atrial arrhythmias (particularly atrial fibrillation)

    • Systolic murmurs

    • Occasionally heart failure

• Clinical Presentations of Graves' disease

  • Common manifestations:

    • Hyperfunctioning goiter

      • Asymmetric, lobular

    • Ophthalmopathy

      • Two components: spastic and mechanical

        • Spastic-- stare, lid lag, lid retraction

        • Poptosis (sensitive to antiadrenergic agents) including:

          1. Ophthalmoplegia

          2. Periorbital swelling

          3. Conjunctivitis

          4. Corneal ulceration, optic neuritis, optic atrophy

    • Diagnosis:

      • In addition to physical manifestations described earlier:

        • Undetectable TSH

        • Usually increased values of T₄ and T₃.

• Thyroid Storm

  • Fulminating increase in symptoms of thyrotoxicosis

  • "Medical storm" is now likely to be seen in undertreated patients.

  • Precipitated by surgery or complicating illness, often sepsis.

  • Presenting syndrome:

    • Extreme irritability

    • Coma or delirium

    • High fever, 41^oC

    • Tachycardia

    • Hypotension

    • Vomiting

    • Diarrhea

  • Treatment:

    • Manage dehydration: IV glucose/Saline, vitamin B complex

    • Glucocorticoids (possible reduction in adrenal reserve; increase glucocorticoid requirement and thyrotoxicosis

    • Digitalis may be required to control elevated ventricular rates in the presence of atrial fibrillation

    • Block hormone synthesis by large dose propylthiouracil; followed by large doses of iodine, oral or parenteral; sodium ipodate may be used instead of iodine

    • Propranolol (adrenergic antagonist) important in the absence of CHF

    • Combination treatment with propylthiouracil, iodine, dexamethasone is likely to result in serum T₃ levels returning to normal within one to two days.

• Thyroid Cancer

  • "The basics of thyroid cancer-Penn State Hershey Cancer Institute"

    Attribution:  Goldenberg D "The basics of thyroid cancer-Penn State Hershey Cancer Institute https://www.youtube.com/watch?v=J7Fes1ByMZM (9/2012) Penn State Health YouTube Channel:  https://www.youtube.com/channel/UCXubLFOt4iiX2_0tYQD8gRA

Greenspan, F.S., and Dong, B. J.. Histamine, Thyroid and Antithyroid Drugs, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 619-633.

Wartofsky, L., Diseases of the Thyroid, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 2012-2034