A 48-year-old woman presents with severe headache. She has a history of refractory hypertension, intermittent headaches, and palpitations. Her vital signs are notable for blood pressure of 242/100 mm Hg and oxygen saturation of 85% on room air. Chest Xray shows diffuse pulmonary edema, and oxygenation improves with high flow nasal cannula. She is admitted to the ICU for blood pressure management and respiratory support. Collection of 24- hour urinary vanillylmandelic acid and metanephrines are started.
Until these results return, which of the following medications would be most appropriate to start to manage her hypertension?
Correct Answer: C
This patient presents in hypertensive emergency secondary to pheochromocytoma. The triad of refractory hypertension, headaches, and palpitations is classic for pheochromocytoma. The diagnosis is confirmed with elevated urinary VMA and metanephrine levels. The essential tenet of pheochromocytoma management is alpha-adrenergic blockade and correction of intravascular volume depletion. The typical agents for alpha blockade are phentolamine and phenoxybenzamine. Phentolamine is available as an intravenous agent and has an onset of action of 1 to 2 minutes, lasting 3 to 10 minutes. Phenoxybenzamine is only available orally and would be inappropriate for immediate blood pressure lowering in this symptomatic patient. Beta-blockade should not be administered initially as the impairment of beta-mediated vasodilation can result in unopposed alpha-mediated vasoconstriction and may lead to circulatory collapse. Thus, labetalol and esmolol are not appropriate first line agents.
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A 72-year-old woman is admitted to the ICU with hypoxemic respiratory failure and sepsis. Her medical history is notable for hypertension, COPD, and CKD (Cr 1.9). Her vital signs are:
She is intubated, undergoes fluid resuscitation and vasopressor support, and receives broad spectrum antimicrobials and is started on a norepinephrine infusion. In addition to routine laboratory studies a thyroid function panel is sent, which is notable for a T3 of 60 ng/dL (normal 80-180) and a TSH 8 µg/dL (normal 0.5-5).
Based on these laboratory studies, which of the following interventions is most appropriate?
Correct Answer: A
This patient presenting with hypoxemic respiratory failure and sepsis has a nonthyroidal illness syndrome (NTIS), which had previously been called the euthyroid sick syndrome. NTIS, which was previously called the euthyroid sick syndrome, is characterized by low T3, usually elevated reverse T3, normal or low TSH, and if prolonged, low T4 levels in clinically euthyroid patients experiencing critical illness (trauma, sepsis, DKA, CKD, malnutrition). A variety of mechanisms have been proposed to explain these thyroid hormone abnormalities, including decreased conversion of T4 to T3, decreased binding to thyroid-binding globulin, and the effect of circulating cytokines and oxidative stress.
Diagnosis of primary hypothyroidism can be difficult in patients who are severely ill and not known to have hypothyroidism before admission to the ICU because serum thyroid hormones, especially T3 , are decreased in most patients in the ICU because of NTIS. In patients clinically suspected to have severe hypothyroidism, the most useful test for diagnosis is measurement of plasma TSH, because a normal plasma TSH excludes primary hypothyroidism. In patients with a combination of primary hypothyroidism and NTIS, serum TSH concentration is still high and responsive to levothyroxine treatment. However, of note is that in patients who have hypothyroidism the high serum TSH concentration might decrease during the acute phase of illness especially if dopamine or high doses of glucocorticoids are given. Thus, high serum TSH in combination with low serum T4 is indicative of hypothyroidism.
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A 48-year-old woman with a history of Grave’s disease undergoes an urgent appendectomy. Four hours after surgery she is found to be confused and diaphoretic. Her vital signs are:
On physical examination there is no evidence of rigidity. An arterial blood gas ABG shows:
Thyroid function tests are sent. Although awaiting the results, which of the following medications would be most appropriate to give?
Correct Answer: B
This patient has thyrotoxicosis (thyroid storm), an acute, life-threatening hypermetabolic state resulting from excessive thyroid hormone. It clinically manifests as altered mental status, fever, tachycardia, and hypertension, which can lead to cardiomyopathy, congestive heart failure, and cardiovascular collapse. In patients with underlying hyperthyroidism it may be precipitated by illness, surgery, or other severe stress. Management is generally supportive with cooling and administration of fluids, as well as measures to inhibit the effects of the excessive thyroid hormones, reduce thyroid hormone synthesis, and prevent further release. The underlying cause of the thyroid storm should also be treated.
Propranolol is effective at blocking the hyperadrenergic manifestations of thyrotoxicosis. Propranolol is a nonselective beta blocker that crosses the blood-brain barrier and is known to decrease the conversion of T4 to T3. Although antipyretic agents should also be administered, aspirin is generally avoided as it may displace thyroid hormone from thyroid binding globulin and exacerbate symptoms. Bromocriptine is a dopamine agonist that is used in treatment of neuroleptic malignant syndrome. Dantrolene expresses excitation-contraction coupling in skeletal muscle by acting as a receptor antagonist to the ryanodine receptor and is the treatment for malignant hyperthermia. Neuroleptic malignant syndrome and malignant hyperthermia are hypermetabolic states that can present similarly to thyrotoxicosis (tachycardia, hyperthermia, altered mental status) but also more commonly result in muscle rigidity, metabolic acidosis, and hypercarbia.
A 48-year-old woman with a history of Grave’s disease undergoes an urgent appendectomy. Fours hours after surgery she is found to have altered mental status and diaphoresis. Her vital signs are:
On physical examination there is no evidence of rigidity. ABG shows:
TSH is <0.01 µg U/mL. Two liters of normal saline and intravenous propranolol are administered.
Which of the following medications is NOT indicated for immediate treatment in this patient?
This patient has thyrotoxicosis (thyroid storm), an acute, life-threatening hypermetabolic state of excessive thyroid hormone. Management is supportive and aimed at blocking further hormone synthesis, release, and peripheral conversion. This thyroid hormone blockade has been referred to as the four ‘Bs’: Beta-blockade; Block synthesis (ie antithyroid drugs); Block release (ie iodine); Block conversion of T4 into T3 (propranolol, corticosteroids).
Thyroid hormone synthesis can be inhibited by either the drugs propylthiouracil (PTU) or methimazole, which prevent the enzyme thyroid peroxidase from iodination of tyrosine residues on thyroglobulin. PTU also inhibits the peripheral conversion of T4 to T3. Even if synthesis is blocked, the thyroid gland still contains stores of thyroid hormone and will continue to release it for days to weeks. To suppress thyroid hormone release, large doses of iodine can be administered. Either potassium iodine or sodium iodine can be used. However, if iodine is administered before blocking thyroid hormone synthesis with an antithyroid agent, it will merely be incorporated into further thyroid hormone production. Therefore, iodine should not be administered for at least 1 hour after PTU or methimazole. Corticosteroids (hydrocortisone) inhibit peripheral conversion of T4 into T3. Moreover, many patients in thyroid storm also have suppression of the HPA axis and are adrenally insufficient.
A 65-year-old woman is admitted to the ICU after being found down at home. Her only medical history is a remote history of Grave’s disease and thyroid ablation. Vital signs are:
On physical examination she obtunded, and brittle hair, macroglossia, and periorbital edema are noted. An ABG shows:
She is intubated for airway protection ventilatory support. Urine, sputum, and blood cultures are sent, and she is treated with broad spectrum antibiotics. Thyroid function tests are sent and she is started on IV levothyroxine.
Which of the following additional therapies is most appropriate at this time?
This patient is in myxedema coma. It is often the result of prolonged noncompliance with thyroid supplementation in the face of absent thyroid function, such as following thyroid ablation. Triggers of myxedema coma include physiologic stresses such as MI and sepsis. Certain drugs that can cause hypothyroidism include amiodarone, propylthiouracil, lithium, and sulfonamides. The hallmark of myxedema is altered mental status and hypothermia, with associated bradycardia and hypotension. On physical examination these patients may have brittle hair, macroglossia, and generalized edema. Laboratory studies of patients with myxedema coma patients may reveal a low PaO2 , high PaCO2 (from blunted respiratory responses), hyponatremia (from impaired free water excretion), hypoglycemia (from hypothyroidism alone or from concomitant adrenal insufficiency), and elevated CPK levels. TSH will also be significantly elevated.
The treatment of myxedema coma should begin based on clinical suspicion and should not await laboratory confirmation. The primary treatment is IV thyroxine, with a loading dose followed by daily administration. Unsuspected adrenal insufficiency is frequently coexisting, and all patients with myxedema coma should also empirically receive hydrocortisone. Insulin administration is not indicated as these patients are commonly hypoglycemic and require supplemental glucose. There is no role for iodine in this patient who has undergone complete thyroid ablation and is receiving IV levothyroxine. Moreover, patients with some intrinsic thyroid function generally do not develop myxedema coma, and the giving high-dose iodine can inhibit thyroid hormone release. Although these patients are profoundly hypothermic, active rewarming is avoided as it can cause peripheral vasodilation and may lead to worsening hypotension and potentially cardiovascular collapse. Passive rewarming is preferred.
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