ACCELERATED HYPERTHYROIDISM OR THYROID STORM IS AN EXTREME ACCENTUATION OF THYROTOXICOSIS Thyroid stom It is an uncommon but serious complication, usually occurring in association with Graves' disease but sometimes with toxic multinodular goiter crisis frequently followed thyroidectomy in hyperthyroid patients The mortality rate due to cardiac failure, arrhythmia, or hyperthermia is as high as 30%, even with treatment.
General: Infection. Non-thyroidal trauma or surgery. Psychosis. Parturition. Myocardial infarction or other acute medical problems. Thyroid specific: Radioiodine. High doses of iodine-containing compounds (for example, radiographic contrast media). Discontinuation of antithyroid drug treatment. Thyroid injury (palpation, infarction of an adenoma). New institution of amiodarone therapy. Precipitating factors in thyroid storm
DELIRIUM, SEVERE TACHYCARDIA, VOMITING, DIARRHEA, DEHYDRATION IN MANY CASES, VERY HIGH FEVER. Clinical features Thyrotoxic crisis is usually of abrupt onset and occurs in patients in whom preexisting thyrotoxicosis has been treated incompletely or has not been treated at all.
RELATED TO CYTOKINE RELEASE AND ACUTE IMMUNOLOGIC DISTURBANCE CAUSED BY THE PRECIPITATING CONDITION. THE SERUM THYROID HORMONE LEVELS IN CRISIS ARE NOT APPRECIABLY GREATER THAN THOSE IN SEVERE UNCOMPLICATED THYROTOXICOSIS, BUT THE PATIENT CAN NO LONGER ADAPT TO THE METABOLIC STRESS. The mechanism by which such factors worsen thyrotoxicosis
NOTE THAT FINDINGS ARE NOT DIFFERENT THAN THAT OF HYPERTHYROIDISM, BUT THE DIFFERENCE IS IN THE SETTING; KEY IS FEVER (TYPICALLY > 40 C / 104 F) YOU CAN BE ADMITTED WITH HYPERTHYROIDISM THAT IS SEVERE YET IS NOT THYROID STORM (HYPERTHYROID TACHYARRHYTHMIAS ARE SERIOUS BUT NOT “STORM”) THYROID HORMONE LEVELS ARE NOT MUCH DIFFERENT IN STORMING THAN IN OTHER CASES SO LIKELY OTHER PREDISPOSING FACTORS (STRESS, METABOLIC FACTORS) Hyperthyroid vs Thyroid Storm
MAJOR PART IS SUPPORTIVE CARE WITH HYDRATION, COOLING BLANKETS, AND ANTIPYRETICS (ACETAMINOPHEN ) management Avoid aspirin (case reports that it releases thyroid hormone from its binding globulin, worsens case) Intensive therapy with anti-thyroid drugs, beta-blockers, steroids, iodine solutions
PROPYLTHIOURACIL , WHICH INHIBITS THYROID HORMONE SYNTHESIS AND CONVERSION OF THYROXINE TO TRI IODOTHYRONINE IS GIVEN BY MOUTH, NASOGASTRIC TUBE, OR RECTALLY AT A RATE OF 300 TO 400 MG EVERY 4–6 HOURS. Anti-thyroid drugs: Carbimazole is less useful since it does not inhibit conversion of thyroxine to tri-iodothyronine. One hour after starting propylthiouracil, iodide ( for example, eight drops of Lugol’s iodine every six hours ) is given to inhibit thyroid hormone release. Alternatively, if available, the radiographic contrast media, sodium ipodate or iopanoic acid, can be given orally, with a loading dose of 2 g followed by 1 g daily. These agents also inhibit conversion of thyroxine to tri-iodothyronine
Theoretically, propylthiouracil should be administered before iodine to inhibit the synthesis of additional thyroid hormone from the administered iodide. Nonetheless, because iodide is the only agent that will block release of preformed thyroid hormones from the thyroid gland and it blocks its own organification through the Wolff-Chaikoff effect, its administration should not be delayed or omitted in the severely toxic patient if propylthiouracil (or methimazole) is not immediately available.
Beta-blockade High doses of b-blocker should be given, and propranolol at a dose of 80–120 mg every six hours is recommended. High output thyrotoxic cardiac failure will respond to control of the heart rate and therefore b-blockade should be used (with caution), while in general the response to digoxin and diuretics is poor. In the absence of cardiac insufficiency or asthma, a β-adrenergic blocking agent should be given to ameliorate the hyperadrenergic state.
If β-adrenergic blocking agents are contraindicated, a calcium channel blocker (diltiazem) may be used to slow the heart rate a very short-acting β-adrenergic blocker such as labetalol or esmolol may be safer than propranolol in this situation High-output congestive heart failure can develop in patients with severe thyrotoxicosis, and a β-adrenergic antagonist may further reduce cardiac output.
Steroids Large doses of dexamethasone (8 mg orally once daily) should be given to support the response to stress, inhibit both the release of hormone from the gland and the peripheral generation of T 3 from T 4 , synergizing with iodide and propylthiouracil, respectively, in these actions. The combined use of propylthiouracil, iodide, and dexamethasone can restore the concentration of T 3 to normal within 24 to 48 hours
Cholestyramine, 4 g every 6–8 hours, binds thyroid hormone in the gut and thus interrupts the modest enterohepatic circulation of thyroid hormone; its use will lead to a more rapid lowering of circulating thyroid hormones Cholestyramine
Supportive measures correction of dehydration and hypernatremia, if present, and administration of glucose Hyperpyrexia should be treated vigorously In mild cases, acetaminophen may suffice, but a cold blanket or ice packs may be required. Salicylates should be avoided because they compete with T 3 and T 4 for binding to TBG and transthyretin (TTR) and therefore increase the free hormone levels. In addition, high doses of salicylates increase the metabolic rate.
If heart failure or pulmonary congestion is present, appropriate diuretics are indicated. In patients with atrial fibrillation, the rapid ventricular response requires appropriate blockade of atrioventricular node conduction.
When treatment is successful, improvement is usually manifested within 1 or 2 days and recovery occurs within a week. At this time, iodide and dexamethasone can be withdrawn and plans for long-term management are made. Follow up After implementation of this four-pronged approach to management of thyrotoxic storm, dramatic clinical improvement is usually seen within 12 to 24 hours in most patients who survive.
Myxedema coma Myxedema coma is a severe, life-threatening sequela of profound hypothyroidism. Myxedema coma is the ultimate stage of severe longstanding hypothyroidism Severe hypothyroidism with metabolic shutdown (cardiac, hepatic, other organs) This state, which almost invariably affects older patients, occurs most commonly during the winter months and is associated with a high mortality rate. Very high mortality 1:3 Typical patient: elderly female with longstanding hypothyroidism.
Clinical features The three main features are: Altered mental state ranging from poor cognitive function through psychosis to coma; Hypothermia (as low as 23˚C) or absence of fever in spite of severe infection (prognosis worsens as the core Temperature fall); The presence of a precipitating event. Hallmark signs of hypothyroidism will be present— dry, coarse, scaly skin; sparse or coarse hair; nonpitting edema of the periorbital regions, hands, and feet; macroglossia; hoarseness; and delayed deep tendon reflexes.
cns manifestations : The patient may have a history of using a CNS depressant, narcotic, or sedative. About 25% of patients with myxedema coma have focal or generalized seizures. Severe sensorial depression, ……coma. CARDIAC MANIFESTATION : Although frank heart failure is rare, cardiomegaly, bradycardia, and decreased cardiac contractility are common features of cardiovascular involvement in myxedema coma. Cardiac enlargement (" myxedema heart" ) is often due to pericardial effusion.
GI tract manifestation : astrointestinal tract involvement in myxedema coma may result in decreased intestinal motility, paralytic ileus, or megacolon, causing patients to present with abdominal pain, constipation, and nausea Oral medications may be ineffective because of these problems. Renal manifestation : Hyponatremia and decreased glomerular filtration rate occur, the kidneys lose their ability to excrete a water load because of decreased delivery of water to the distal nephron, as well as increased production of antidiuretic hormone.
Biochemical abnormalities hyponatraemia, normal or increased urine sodium excretion raised creatine phosphokinase and lactate dehydrogenase, hypoglycaemia normocytic or macrocytic anaemia Thyroid stimulating hormone values may only bemodestly raised (and will be normal or low in secondary hypothyroidism) but free thyroxine levels are usually very low.
Three major etiologies: Undiagnosed hypothyroidism (autoimmune thyroiditis, radiation hypothyroidism, etc) More commonly discontinuation of therapy or running out of medication (for months) Iatrogenic: stopping patients for I-131 cancer Rx
MANAGEMENT The importance of the difficulty in diagnosing myxedema coma is that a delay in therapy worsens the prognosis Consequently, the diagnosis should be made on clinical grounds, and, after sending serum for thyroid function tests, therapy should be initiated without awaiting the results of confirmatory tests because mortality may be 20% or higher. Even with prompt recognition and treatment, mortality is 20%–30%.
The three principles of management are 1. Rapid institution of thyroid hormone replacement, 2. Treatment of the precipitating cause, and 3. provision of ventilatory and other support. ‘‘ High dose’’ regimens may be given as follows: if intravenous thyroxine is available, this can be given as a bolus of 300–500 mg, followed by 50–100 mg daily. Oral thyroxine in similar doses can be given (usually by nasogastric tube), but absorption may be impaired. thyroid hormone replacement
There is a theoretical concern that conversion of thyroxine to triiodothyronine will be impaired due to the effects of any illness on deiodinase activity, and therefore the use of triiodothyronine instead of thyroxine has been advocated, but this also has the potential to cause adverse cardiac effects when given too rapidly. The usual intravenous dose of triiodothyronine is 10–20 mg initially, followed by 10 mg every four hours for 24 hours, then 10 mg every six hours. Oral treatment with similar doses is also possible. A further variation is to give 200 mg thyroxine with 10 mg triiodothyronine initially, and then tri-iodothyronine 10 mg every 12 hours and thyroxine 100 mg every 24 hours, until the patient resumes normal thyroxine orally.
The authors recommend ECG monitoring and careful titration of thyroid replacement therapy against any definite ischaemic ECG abnormalities. steroid Hydrocortisone (5 to 10 mg/hr) should also be given because of the possibility of relative adrenocortical insufficiency as the metabolic rate increases. ANTIBIOTICS Treatment of the underlying precipitant is usually straightforward. Broad spectrum antibiotics should be considered if there is no obvious cause, as the signs of an infection may be obscure, yet this is the underlying cause in up to a third of cases.
OTHER S A critical element in therapy is support of respiratory function by means of assisted ventilation and controlled oxygen administration All patients should be admitted to intensive care or the HDU: most patients require ventilatory support for 1–2 days. Hypothermia should be treated with space blankets, since active external rewarming leads to circulatory collapse due to peripheral vesodilatation. Cautious volume expansion using intravenous saline usually suffices, but hypertonic saline may need to be considered if the serum sodium is very low (,120 mmol/l)
Intravenous glucose may be required for hypoglycaemia. General measures applicable to the comatose patient should be undertaken, such as frequent turning, prevention of aspiration, and attention to fecal impaction and urinary retention. Finally, the physician should assess the patient for the presence of coexisting disease, such as infection and cardiac or cerebrovascular disease. In particular, the myxedematous patient may be afebrile despite a significant infection. As soon as the patient is able to take medication by mouth, treatment with oral levothyroxine should be instituted
Pituitary apoplexy is caused by haemorrhagic infarction of a pituitary tumour or less commonly the normal pituitary gland Acute pituitary apoplexy This may cause volume expansion with local mass effect. Apoplexy is an endocrine emergency that may result in severe hypoglycemia, hypotension, central nervous system (CNS) hemorrhage, and death. Prompt recognition is needed to prevent cardiovascular collapse secondary to pituitary-adrenal hypofunction. There is an equal sex incidence.
Pituitary apoplexy may occur spontaneously in a preexisting adenoma; post-partum (Sheehan's syndrome); or in association with diabetes, hypertension, sickle cell anemia, or acute shock The hyperplastic enlargement of the pituitary during pregnancy increases the risk for hemorrhage andinfarction.
Clinical features These resemble those of subarachnoid haemorrhage , severe headache, nausea (80%), vomiting (60%), photophobia(50%), and loss of consciousness (10%). Neuro-ophthalmic signs include ocular paresis in up to 70% of cases with IIIrd (67%), IVth (4%), and Vth (29%) nerve palsies, Visual field defects, and even blindness. Pre-existing endocrine dysfunction is present in 20%–30%. patient may have circulatory collapse.
Management If pituitary apoplexy is suspected (or confirmed by urgent magnetic resonance imaging or computed tomography), hydrocortisone 100 mg intramuscularly six hourly, or 4 mg/ hour intravenously should beadministered without delay and continued until the crisis is over. Those with significant or progressive visual loss or loss of consciousness require urgent surgical decompression. Visual recovery after surgery is inversely correlated with the length of time after the acute event. Therefore, severe ophthalmoplegia or visual deficits are indications for early surgery.
Early neurosurgical intervention is associated with improved neuro-ophthalmic outcome with reported improvements in visual acuity and fields of 86% and 76% respectively.
1. Following Stress (trauma, surgery, infection, or prolonged fasting) in patient with latent insufficiency. 2. Following sudden withdrawal of adrenocortical hormone in a patient with chronic insufficiency 3. Following bilateral adrenalectomy or a functioning adrenal tumor that had suppressed the other adrenal 4. Following sudden destruction of the pituitary gland (pituitary necrosis) or when thyroid hormone is given to a pt with hypoadrenalism 5. Following injury to both adrenals by trauma, hemorrhage, anticoagulant therapy, thrombosis, infection, or metastatic carcinoma. Cooper MS, Stewart PM. Corticosteroid insufficiency in acutely ill patients. N Engl J Med 2003;348:727-734 Causes
Dehydration, hypotension, or shock out of proportion to severity of current illness Nausea and vomiting with a history of weight lost and anorexia Abdominal pain, so-called acute abdomen Unexplained hypoglycemia Unexplained fever CLINICAL AND LABORATORY FEATURES OF AN ADRENAL CRISIS Hyponatremia, hyperkalemia, azotemia, hypercalcemia, or eosinophilia Hyperpigmentation or vitiligo Other autoimmune endocrine deficiencies, such as hypothyroidism or gonadal failure
Not influenced by diurnal variations in cortisol secretion.
Baseline cortisol sample. ACTH 250mcg. Post-ACTH plasma cortisol at 30min and 60min p injection.
Baseline above 34 is normal and less than 15 is evidence of insufficiency. When between the two, the incriment increase with ACTH should be greater than 9mcg/dL.
TREATMENT OF ACUTE ADRENAL INSUFFICIENCY (ADRENAL CRISIS) EMERGENCY MEASURE 1. Establish intravenous access with a large-gauge needle. 2. Draw blood for stat serum electrolytes and glucose and routine measurement of plasma cortisol and ACTH. Do not wait for laboratory results. 3. Infuse 2 to 3 L of 154 mmol/L NaCl (0.9% saline) solution or 50 g/L (5%) dextrose in 154 mmol/L NaCl (0.9% saline) solution as quickly as possible. Monitor for signs of fluid overload by measuring central or peripheral venous pressure and listening for pulmonary rales. Reduce infusion rate if indicated. 4. Inject intravenous hydrocortisone (100 mg immediately and every 6 hr) 5. Use supportive measures as needed.
SUBACUTE MEASURES AFTER STABILIZATION OF THE PATIEN 1. Continue intravenous 154 mmol/L NaCl (0.9% saline) solution at a slower rate for next 24 to 48 hr. 2. Search for and treat possible infectious precipitating causes of the adrenal crisis. 3. Perform a short ACTH stimulation test to confirm the diagnosis of adrenal insufficiency, if patient does not have known adrenal insufficiency. 4. Determine the type of adrenal insufficiency and its cause if not already known. 5. Taper glucocorticoids to maintenance dosage over 1 to 3 days, if precipitating or complicating illness permits. 6. Begin mineralocorticoid replacement with fludrocortisone (0.1 mg by mouth daily) when saline infusion is stopped.