**6.6 Supportive and resuscitative measures**

*Goiter - Causes and Treatment*

is thyroidectomy.

4–5 days [74].

mixing 1 g of iodide in 60 mL of water and administering 2 g/day in divided doses [70]. Lugol's solution can be given rectally in doses of 4 mL (80 drops) per day [71]. Iodine should be given at least 30 min after administering thionamides to avoid the iodine serving as a substrate for new thyroid hormone production and worsening the hyperthyroidism. Thionamides must be continued during therapy with iodine to avoid organification of iodine and increased thyroid hormone production. Iodine administration delays definitive treatment of patients' hyperthyroidism with radioactive iodine [27, 28]. Therefore, iodine should be used only when the end goal

Lithium hampers T4 and T3 synthesis by inhibiting the coupling of iodotyrosine residues. When iodine administration is not possible (secondary to iodine induced anaphylaxis) or desired, lithium may be substituted. It is administered at doses of

The next line of treatment is inhibiting the release of preformed hormone. Iodine administration, additionally, blocks the release of preformed hormone by inhibiting the release of iodothyronines (T3 and T4) from thyroglobulin [28, 72]. This effect of iodine has a faster onset than PTU, which blocks synthesis in a thyroid gland that has a large store of already formed hormone [73]. The combination therapy of thionamides and iodine decrease serum T4 levels to normal range in

Both α- and β-adrenergic stimulation are enhanced in thyroid storm. Thus, adrenergic blockade is an integral part of the treatment. β-Blockers have been used in treatment of both uncomplicated and complicated hyperthyroidism [75]. Propranolol is the most commonly used β-blocker due to its nonselective β-adrenergic antagonism and its ability to block the peripheral conversion of T4 to T3. The recommended dose is 60–120 mg orally every 6 h [64]. For a more rapid effect, intravenous propranolol or a shorter acting β-blocker such as esmolol can be used. The dose of intravenous propranolol is 0.5–1.0 mg slow infusion for an initial dose and then 1–2 mg at 15-min intervals while monitoring the heart rate carefully. Esmolol is given as an initial bolus of 0.25–0.5 mg/kg followed by a continuous

300 mg every 6–8 h with monitoring of serum levels.

**6.3 Inhibiting the peripheral effect of thyroid hormone**

infusion rate of 0.05–0.1 mg/kg per minute [73].

**6.4 Inhibiting enterohepatic circulation of thyroid hormone**

Enterohepatic circulation of thyroid hormone is targeted for severe and refractory thyroid storm. Thyroid hormone is metabolized in the liver where it is conjugated to glucuronides and sulfates. Conjugated products are excreted into the intestine through bile, where free hormones are released, reabsorbed, and circulated. This is enterohepatic circulation of thyroid hormone. Cholestyramine binds the conjugation products and promotes their excretion, and can be used to decrease thyroid hormone levels. The recommended dose is 1–4 g twice a day [76–78].

The oral iodinated contrast agents are inhibitors of both deiodinases D1 and D2 and help in lowering T3 levels. Additionally, they inhibit new thyroid hormone

**6.2 Inhibiting thyroid hormone release**

**122**

**6.5 Other therapies**

Resuscitative measures should be initiated immediately in an ICU setting. Urgent addressal of systemic decompensation requires correction of hyperthermia, dehydration, congestive heart failure, dysrhythmia, and prevention of adrenal crisis [73]. Hyperthermia should be controlled with peripheral cooling and antipyretics. Acetaminophen is preferred over salicylates as salicylates increase free hormone levels by decreasing binding to T4-binding globulin, thereby exacerbating thyroid storm [83]. The peripheral cooling should be done with ice packs, cooling blankets, or alcohol sponges. Fluid loss due to hyperpyrexia, diarrhea, and vomiting should be corrected immediately.

The hypothalamo-pituitary-adrenal axis is impaired in thyrotoxicosis with a decrease in adrenal reserve. Despite increased production of cortisol by the adrenal gland to compensate for accelerated glucocorticosteroid metabolism in hyperthyroid states, a subnormal response of the adrenal glands to adrenocorticostimulating hormone occurs. Corticosteroids are therefore used as adjunct therapy in thyroid storm to prevent adrenal insufficiency. It also helps in decreasing the peripheral conversion of T4 to T3 [84]. A loading dose of 300 mg of hydrocortisone intravenously followed by 100 mg every 8 h is recommended [67].

The treatment of thyroid storm is not complete and effective until correctable precipitating factors are addressed (**Table 1**). Any focus of infection should be thoroughly investigated and proper antibiotics should be started based on sensitivity. In addition, any metabolic abnormalities, such as diabetic ketoacidosis, stroke, or pulmonary emboli, should be treated as per standard protocols.

## **6.7 Therapeutic plasma exchange**

In refractory cases of thyrotoxic crisis with no clinical improvement alternative measures to clear thyroid hormone from the circulation should be instituted. Therapeutic plasma exchange (TPE) is effective in rapidly reducing thyroid hormone levels [85]. The patient's plasma is extracted from the components of blood, and replaced with albumin or fresh frozen plasma [85, 86]. TBG with bound thyroid hormone is removed from circulation, and the colloid replacement (usually albumin) provides unsaturated binding sites for circulating free thyroid hormone. Various techniques of exchange transfusion have evolved since its first description in 1970 by Ashkar et al. [87]. Plasma exchange, single pass albumin dialysis, and charcoal hemoperfusion have all demonstrated a reduction in free T3 and free T4 levels [85].

TPE is an option when clinical deterioration in thyroid storm occurs despite the use of first- and second-line therapies. Muller et al. suggested early initiation of TPE with the following indications: severe symptoms (cardio-thyrotoxicosis, neurologic manifestations, and severe myopathy); rapid clinical deterioration; contraindications to other therapies; and failure of conventional therapeutics [88]. The American Society for Apheresis (ASFA) recommends that TPE be performed at a frequency of daily to every 2–3 days until clinical improvement is noted. Complications of TPE are seen in 5% of patients and include hypotension, hemolysis, allergic reactions, coagulopathy, vascular injury, and infection [86, 88, 89].


**Table 7.** *Indications of surgery.*
