04. Hyperthyroidism, Thyrotoxicosis, and Thyroid Storm

Definition 

  • Hyperthyroidism occurs when there is accelerated thyroid hormone biosynthesis and secretion by the thyroid gland.
  • Thyrotoxicosis is the hypermetabolic clinical syndrome resulting from serum elevations in thyroid hormone levels, specifically free thyroxine (FT4) and/or triiodothyronine (FT3).
  • Thyroid storm is the extreme manifestation of thyrotoxicosis that is life-threatening and a medical emergency, often precipitated by surgery, trauma, or infection.

Etiologies

  • Graves’ disease (diffuse toxic goiter): most common cause. Diffuse enlargement of thyroid,       ± exophthalmos, ± dermopathy (pretibial myxedema) with TSH-receptor auto-antibodies (TRAb). Can be associated with other autoimmune disorders (e.g. T1DM, pernicious anemia).  Risk factors are not well-defined but may include genetic factors, high iodine intake, stress, smoking, and the postpartum state.
  • Toxic adenoma/toxic multinodular goiter: hyperplasia of thyroid follicular cells due to activating mutations; independent of TSH. Sometimes associated with low iodine intake.
  • Subacute thyroiditis: often due to viral infection. Thyrotoxicosis due to release of stored thyroid hormone, followed by euthyroid and/or hypothyroid phases, then recovery. May be painful (de Quervain’s) or painless (subacute lymphocytic thyroiditis, post-partum thyroiditis).
  • Other causes: iodine load-induced (the Jod-Basedow phenomenon), exogenous ingestion (thyrotoxicosis factitia), struma ovarii (thyroid tissue in ovarian tumor), pituitary TSH-secreting adenoma, early Hashimoto’s (hashi-toxicosis), amiodarone-induced, trophoblastic tumors (hCG stimulation of TSH receptor).

Evaluation

Symptoms and signs

  • Signs of hypermetabolic state: restlessness, tachycardia, diaphoresis, hyper-defecation, weight loss, palpitations. Can also see lid lag, heat intolerance, tremor, hyperreflexia, moist skin and fine hair.
  • Apathetic hyperthyroidism: elderly patients often don’t have classic symptoms, but may present with lethargy, weight loss, shortness of breath and atrial fibrillation.

Associated conditions/complications

  • Heart failure, osteoporosis, hypercalcemia, nephrolithiasis. May account for 10-15% of new cases of atrial fibrillation.

Thyroid storm (severe thyrotoxicosis)

  • Fever (often very high 104-106ºF), delirium, stupor, coma, diaphoresis, tachycardia, arrhythmias, CHF, vomiting/diarrhea, hepatic failure.
  • Often induced by illness, surgery, or iodine administration, can also be seen with long untreated hyperthyroidism.

Work-up

  • TSH suppressed (except in pituitary disease), FT4 and/or FT3 increased.
  • ESR can be increased in subacute thyroiditis.
  • Anti-thyroperoxidase antibodies often positive in silent thyroiditis.
  • TSH receptor Ab (TRAb) positive in Graves’ disease.  
  • Radioactive iodine uptake can be useful to differentiate between causes (contraindicated in pregnant patients): diffuse high uptake in Graves’, focal high uptake with toxic nodule(s), very low uptake in subacute thyroiditis.
  • Burch-Wartofsky Point Scale (BWPS) is a scoring system to help identify thyroid storm.

Management

Medical therapy

  • Up to 50% of patients with Graves’ disease can go into spontaneous remission.
  • Symptom management: propranolol to control symptoms and tachycardia (blocks adrenergic effects and peripheral conversion of T4 to T3). Beta blockade can be stopped once anti-thyroid treatment takes effect.
  • Inhibition of hormone synthesis: methimazole or propylthiouracil (PTU). May be used as short-term management until definitive therapy, or for long-term use. Methimazole is generally preferred due to better side effect profile (PTU preferred in pregnancy). Risk of agranulocytosis, seen in 0.5%, usually early in treatment, also risk for hepatic toxicity. Obtain baseline CBC and LFTs.

Definitive therapy

  • Radioactive iodine ablation with I-131 or surgery, generally rendering patient hypothyroid and requiring thyroid hormone replacement.

Thyroid storm

  • Consult Endocrinology as mortality is 10-20%.
  • Supportive therapy with IVF, O2, and acetaminophen, likely ICU.
  • Careful search for precipitating causes (e.g. infection). Avoid ASA, as it can displace FT4 from TBG.
  • Immediately start PTU 200-300 mg PO q 4-6 hours.
  • Follow with saturated solution of potassium iodide (SSKI) to inhibit conversion of T4 to T3.
  • Consider propranolol 60-80 mg PO q 4-6 hours to control tachycardia (caution in heart failure).
  • Consider hydrocortisone 50-100 mg IV q 6-8 hours x 48 hours (blocks conversion of T4 to T3).

Key Points

  • Most hyperthyroidism is caused by Graves’ disease.
  • Hyperthyroidism can manifest as atrial fibrillation, CHF, osteoporosis, or weight loss/fatigue in elderly.
  • Treatment consists of propanolol, thionamides, radioactive ablation, or surgery.
  • Thyroid storm is a clinical emergency and prompt diagnosis and treatment are essential.

Brent GA. Grave’s Disease. NEJM. 2008; 358:2594-605.

Cooper DS. Antithyroid drugs. NEJM 2005; 352:905-17.

Nayak B. Thyrotoxicosis and Thyroid Storm. Endocrinol and Metab Clin 2006; 35(4):663-686

Ross DS, Burch HB, Cooper DS, et al.  2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of

Thyrotoxicosis. Thyroid. Oct 2016.1343-1421. http://doi.org/10.1089/thy.2016.0229.