Acute Adrenal Insufficiency

Causes:

➧ Usually presents as an acute process in a patient with underlying chronic adrenal insufficiency

➧ Causes of Primary adrenal insufficiency:

   - Auto-immune

   - TB of adrenals

   - Metastatic malignancy to adrenals

➧ Causes of Secondary or Tertiary adrenal insufficiency

   - Pituitary or hypothalamic disease

➧ Acute destruction of the adrenals can occur with bleeding in the adrenals:

   - Sepsis

   - Disseminated intravascular coagulopathy (DIC)

   - Complication of anticoagulant therapy

Precipitating factors:

➧ Omission of medication

➧ Precipitating illness:

   - Severe infection

   - Myocardial infarction

   - Cerebro-vascular accident (CVA)

   - Surgery without adrenal support

   - Severe trauma

➧ Withdrawal of steroid therapy in a patient on long term steroid therapy (Adrenal atrophy)

➧ Administration of drugs impairing adrenal hormone synthesis e.g. Ketoconazole

➧ Using drugs that increase steroid metabolism e.g. Phenytoin and Rifampicin

Clinical picture:

➧ Nausea and vomiting

➧ Hyperpyrexia

➧ Abdominal pain

➧ Dehydration

➧ Hypotension and shock

Clues to underlying Chronic Adrenal Insufficiency:

➧ Pigmentation in unexposed areas of the skin:

   - Creases of hands

   - Buccal mucosa

   - Scars

➧ Consider adrenal insufficiency if hypotension does not respond to pressors

Laboratory diagnosis:

➧ Hyponatremia and hyperkalemia (Hyponatremia might be obscured by dehydration).

➧ Random cortisol is not helpful unless it is very low (less than 5 mg/L) during a period of great stress.

➧ ACTH (Cosyntropin) stimulation test:

- Failure of cortisol to rise above 552 nmol/L 30 min after administration of 0.25 mg of synthetic ACTH IV

➧ Basal ACTH will be raised in primary adrenal insufficiency but not in secondary.

➧ CT of the abdomen will reveal enlargement of adrenals in patients with adrenal hemorrhage, active TB, or metastatic malignancy.

Management of Acute Adrenal Insufficiency:

➧ Hydrocortisone: 200 mg IV stat then 100 mg/8 h. for 24 h

-Taper slowly over the next 72 h.

-When oral feeds are tolerated change to oral replacement therapy.

-Overlap the first oral and last IV doses.

➧ Dexamethasone: 10 mg/6 h. IV

➧ Fludrocortisone: 0.05-0.3 mg/d. (if hydrocortisone less than 100 mg/d).

-Patients with primary adrenal insufficiency may require mineralocorticoid therapy (fludrocortisone) when shifted to oral therapy.

➧ 5% dextrose: IV for hypoglycemia

➧ Normal saline: IV for volume expansion

➧ Treat precipitating diseases

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Thyroid Storm

Definition:

➧ Acute life-threatening exacerbation of thyrotoxicosis

Precipitating factors:

➧ Withdrawal of antithyroid drugs

➧ Severe infection

➧ Diabetic ketoacidosis (DKA)

➧ Cerebro-vascular accident (CVA)

➧ Cardiac failure

➧ Surgery

➧ Trauma 

➧ Radioiodine

➧ Drug reaction

➧ Iodinated contrast medium

Clinical picture:

➧ Patient with Graves disease who has discontinued antithyroid medication OR is previously undiagnosed

➧ Hyperpyrexia (40ºC)

➧ Sweating

➧ Tachycardia with or without AF

➧ Nausea, vomiting, and diarrhea

➧ Tremulousness and delirium, occasionally apathetic

Diagnosis:

➧ Free T4, free T3 elevated

➧ TSH suppressed

➧ Note that findings are not different than that of hyperthyroidism, but the difference is in the setting

Management of Thyroid Storm:

1-Inhibition of hormone production:

➤ Antithyroid agents:

➧ Thionamides (1st line therapy):

➧ Carbimazole/Methimazole 20-25 mg/6 h. orally or rectally (although once stable, the frequency of dosing can be decreased to once or twice daily).

-Carbimazole is metabolized to methimazole after ingestion.

-Halt synthesis of thyroid hormone by interfering with thyroid peroxidase.

➧ Propylthiouracil (PTU): 200 mg or 300 mg/6 h.

-Blocks peripheral conversion of T4 to T3 through inhibition of type 1 deiodinase.

2-Inhibition of thyroid hormone release:

➤ Iodine: (high concentration) 0.2-2 g/ d.

-Blocks release a stored hormone (Wolff-Chaikoff effect).

-Decreases iodide transport.

-Prevents oxidation in follicular cells.

-Iodine is given 1 hr after PTU to prevent incorporation into a new hormone.

-Above effects are only transient (48 h.).

-Lower concentration accelerates thyroid metabolism.

➧ Lugol’s solution: (assuming 20 drops/mL, 8 mg iodine/drop) 4-8 drops/6-8 h. oral.

➧ Potassium iodide: (with 20 drops/mL, 38 mg iodide/ drop) 5 drops/6 h.

➧ Oral iodinated contrast agents: 

-Competitively inhibit Types 1 and 2 50-monodeiodinase in the liver, brain, and thyroid, blocking the conversion of T4 to T3, resulting in a rapid decrease in T3 and an increase in reverse T3. 

-Inhibit binding of T3 and T4 to cellular receptors. 

➧ Sodium ipodate: (308 mg iodine/500mg capsule) 1-3 g/ d.

➧ Iopanoic acid: 1g/8 h. for the first 24 hours, followed by 500 mg/12 h.

3-Controlling of cardiovascular manifestations:

➤ β-blockers:

-Control cardiovascular and hyperadrenergic manifestations.

-Decrease T4-T3 conversion.

➧ Propranolol: 60 to 80 mg/4 h., or 80 to 120 mg/4 h.

-The onset of action after oral dosing takes place within 1 hour. 

➧ For a more rapid effect, propranolol can also be administered parenterally, with a bolus of 0.5-1 mg over 10 min. followed by 1-3 mg over 10 min., every few hours, depending on the clinical context.

-Relatively large doses of propranolol are required in the setting of thyrotoxicosis because of the faster metabolism of the drug, and possibly because of a greater quantity of cardiac beta-adrenergic receptors.

➧ Esmolol: 50-100 µg/kg/min. IV.

➧ Longer-acting cardioselective β-adrenergic receptor antagonists: such as ➧ Atenolol and Metoprolol may be used also.

➤ Anticoagulation of AF:

➧ One of the significant cardiovascular complications of thyrotoxicosis is atrial fibrillation, occurring in 10% to 35% of cases. In the largest retrospective study, it appears that thyrotoxic patients who have atrial fibrillation are not at greater risk for embolic events, compared with age-matched patients who have atrial fibrillation due to other causes.

➧ Standard therapy with warfarin or aspirin is indicated, according to standard guidelines for atrial fibrillation.

➧ Thyrotoxic patients may require a lower maintenance dose of warfarin than euthyroid patients because of increased clearance of vitamin K-dependent clotting factors.

4-Steroids:

➤ Hydrocortisone: 100mg /8 h. IV with tapering as the signs of thyroid storm improve.

- Decreases T4-T3 conversion.

5-Alternative therapies:

-Several therapeutic agents used in the treatment of thyrotoxicosis are only considered when the first-line therapies of thionamides, iodide, beta-blockers, and glucocorticoids fail or cannot be used owing to toxicity.

➤ Potassium perchlorate: 1g qid oral

-Amiodarone induced thyrotoxicosis

-Inhibits iodide uptake by the gland.

➤ Lithium: 300 mg/8 h. 

-When thionamide is contraindicated.

-Inhibits new hormone synthesis.

-Decreases hormone secretion.

-To avoid lithium toxicity, lithium levels should be monitored regularly (perhaps even daily) to maintain a concentration of about 0.6-1.0 mEq/L.

➤ Guanethidine: 30-40 mg/6 h. orally

➤ Reserpine: 2.5-5 mg/4 h. IM

- Before β-adrenergic receptor antagonists were used to counteract the peripheral effects of thyroid hormone, the antiadrenergic agents, reserpine and guanethidine, were often used.

-Reserpine is an alkaloid agent that depletes catecholamine stores in sympathetic nerve terminals and the central nervous system.

- Guanethidine also inhibits the release of catecholamines.

-Side effects of these medications include hypotension and diarrhea. Reserpine can also have central nervous system depressant effects.

-These agents are indicated only in rare situations where β-adrenergic receptor antagonists are contraindicated, and when there is no hypotension or evidence of central nervous system-associated mental status changes

➤ Cholestyramine: 4 g four times a day oral.

-Decreases enterohepatic reabsorption of thyroid hormone.

➤ Plasmapheresis:

-When clinical deterioration occurs in thyroid storm, despite the use of all of these medications, removal of thyroid hormone from circulation would be a therapeutic consideration. Plasmapheresis, charcoal hemoperfusion, resin hemoperfusion, and plasma exchange are effective in rapidly reducing thyroid hormone levels in thyroid storms.

6-Supportive care:

➤ Supportive care is an important part of the multisystem therapeutic approach to thyroid storm.

➤ Antipyretics should be used; paracetamol is the preferable choice. Salicylates should be avoided in thyrotoxicosis because salicylates can decrease thyroid protein binding, causing an increase in free thyroid hormone levels. External cooling measures can also be used.

➤ Fluid loss and dehydration are also common in severe thyrotoxicosis. The fluid losses could result from the combination of fever, diaphoresis, vomiting, and diarrhea.

➤ Intravenous fluids with dextrose: (isotonic saline with 5% or 10% dextrose) should be given to replenish glycogen stores.

➤ Multivitamins, particularly thiamine, to prevent Wernicke's encephalopathy, which could result from the administration of intravenous fluids with dextrose in the presence of thiamine deficiency.

➤ If indicated digoxin for congestive heart failure.

➤ Treating the precipitating cause of thyrotoxicosis is particularly important, considering that the most common precipitant is thought to be an infection.

Prognosis:

➧ Mortality dropped since the 1920s from 100% to 20 – 30%

➧ Mortality is most frequently associated with serious underlying medical conditions 

Read more ☛ Myxedema Coma

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Myxedema Coma

Definition:

➧ The end-stage of untreated or insufficiently treated hypothyroidism.

Pathogenesis of Myxedema: (Figure 1)

Figure 1: Pathogenesis of Myxedema Coma

Precipitating factors:

➧ CVA

➧ Myocardial infarction

➧ Infection (UTI, Pneumonia)

➧ Gastrointestinal hemorrhage

➧ Acute trauma

➧ Administration of sedative, narcotic or potent diuretics

Typical clinical picture:

➧ Elderly obese female

➧ Becoming increasingly withdrawn, lethargic, sleepy, and confused

➧ Slips into a coma

History:

➧ Previous thyroid surgery

➧ Radioiodine

➧ Default thyroid hormone therapy

Physical findings:

➧ Comatose or semi comatose

➧ Dry coarse skin

➧ Hoarse voice

➧ Thin dry hair

➧ Delayed reflex relaxation time

➧ Hypothermia

➧ Pericardial, pleural effusions, ascites

Laboratory tests:

➧ Free T4 low and TSH high

➧ If the T4 is low and TSH low normal consider pituitary hypothyroidism

➧ Blood gases

➧ Electrolytes and creatinine 

➧ Distinguish from the euthyroid sick syndrome

➧ Low T3, Normal or low TSH, normal free T4

ECG in a patient with Myxedema Coma: (Figure 2)

Figure 2: ECG in Myxedema Coma

Management of Myxedema:

➧ ICU admission: may be required for ventilatory support and IV medications.

➧ Parenteral thyroxine: Loading dose of 300-500 μg IV, then 50-100 μg/d. IV or 100-200 μg/d. oral

➧ Glucocorticoids: Hydrocortisone: 100 mg/8 h. for 1 week, then taper.

-Controversial but necessary in hypopituitarism or multiple endocrine failures.

➧ Electrolytes:

-Water restriction for hyponatremia 

-Avoid fluid overload

➧ Avoid sedation

Prognosis:

➧ Mortality is 20% and is mostly due to underlying and precipitating diseases.

Read more ☛ Thyroid Storm

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