Etiology | Unique clinical manifestations and clues (IN ADDITION TO the typical manifestations of a hyperadrenergic state) | Risk factors and diagnostic tools |
Common causes | ||
Hypoglycemia | Neuroglycopenia can cause confusion, altered mental status, or focal neurologic deficits mimicking stroke | Low glucose measurement* |
Acute decompensated heart failure with preserved ejection fraction (HFpEF, "flash pulmonary edema")¶ | Hypoxia, respiratory distress, crackles, or wheezes | Chest radiograph with pulmonary edema, cardiomegaly, upper zone redistribution of blood flow Past medical history of cardiac disease or hypertension BNP or NT-proBNP elevated |
Myocardial ischemia/infarction | Chest pain, dyspneaΔ | ECG with abnormalities consistent with ischemia or infarction Elevated cardiac biomarkers |
Intoxications◊ | History of ingestion or use Urine drug screen is not diagnostic as only tests for recent use and not intoxication | |
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| Horizontal, vertical, or rotary nystagmus | |
| Hypokalemia and hyperglycemia can occur Serum concentration available at some hospital laboratories | |
| Flushed but dry skin, dry lips, mumbling speech | Delirium, if present, improves with physostigmine |
Withdrawal syndromes | History of chronic use and recent cessation or dose decrease | |
| AST/ALT ratio is often >2:1 | |
| Yawning, lacrimation, rhinorrhea, piloerection | |
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| May not improve with benzodiazepines | |
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Thyrotoxicosis | Thyroid enlargement, exophthalmos, periorbital and conjunctival edema, lid lag, thin hair, proximal muscle weakness, hyperreflexia | Low TSH and high free T4 and/or T3 |
Serotonin toxicity (serotonin syndrome) | Clonus and/or hyperreflexia in legs | Temporally associated with initiation or increase of serotonergic drug Diagnosed by Hunter criteria§ |
Meningitis/encephalitis/meningoencephalitis | Fever, severe headache, stiff neck, nausea | Cerebrospinal fluid tests consistent with infection |
Envenomations¥ | ||
| Muscle spasm and pain, abdominal pain and wall rigidity | Recent history of outdoor or garage activity Bite appears as a blanched circular patch with a surrounding red perimeter and a central punctum ("target" lesion) |
| Roving eye movements, hypersalivation | Tapping the sting site may exacerbate the pain ("tap test"), but typically no local inflammation is present CK elevation can be seen with severe envenomation |
| Pulmonary edema, myocardial dysfunction | Stings often cause local pain, paresthesias, and central puncta with swelling, erythema, and localized piloerection |
| Immediate localized pain then delayed onset of severe generalized back, chest, and abdominal pain | Swimming in waters known to harbor box jellyfish Linear, red, urticarial lesions at sting site |
| Paresthesias, fasciculations (especially tongue), hypersalivation, pulmonary edema | Painful bite because of large fangs |
Uncommon causes | ||
Pheochromocytoma | Hypertension can be sustained or paroxysmal, episodic headache, sweating | Measurements of urinary and/or plasma fractionated metanephrines and catecholamines |
Hypercortisolism (severe) | Plethora, round face, hirsutism, striae, easy bruising, proximal muscle weakness | Bedtime salivary cortisol, 24-hour urinary free cortisol excretion, or overnight dexamethasone suppression test |
Neuroleptic malignant syndrome | Signs develop over days to weeks "Lead pipe" rigidity, bradykinesia | Use of antipsychotic agents CK typically >1000 IU/L; can be as high as 100,000 IU/L |
Malignant hyperthermia-like episodes | Unexplained stress-induced fever, muscle cramping, or rigidity unrelated to anesthesia exposure | Contracture testing (bioassay of skeletal muscle) |
Autonomic dysreflexia | Attacks of loss of coordinated autonomic responses typically triggered by noxious stimuli | Spinal cord injury above T6 |
Autoimmune or paraneoplastic encephalitis | Assessment of the cerebrospinal fluid | |
Familial dysautonomia (Riley-Day syndrome) | Sensorimotor neuropathy, smooth tongue that lacks fungiform papillae | Mainly in patients of Ashkenazi Jewish decent Diagnosed by genetic evaluation |
Acrodynia (mercury toxicity; "Pink disease") | Children with lip and hand edema and erythema, skin desquamation | Elevated blood and urine mercury concentrations |
25I-NBOMe: 4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine; 2C-B: 4-Bromo-2,5-dimethoxyphenethylamine; ALT: alanine transaminase; AST: aspartate transaminase; BNP: B-type natriuretic peptide; CK: creatine kinase; ECG: electrocardiogram; GHB: gamma-hydroxybutyrate; LSD: lysergic acid diethylamide; MDMA: 3,4-Methylenedioxymethamphetamine ("ecstasy"); NT-proBNP: N-terminal pro-BNP; PCP: phencyclidine; T3: triiodothyronine; T4: thyroxine; TSH: thyroid-stimulating hormone.
* Autonomic signs and symptoms typically develop with serum glucose <55 mg/dL (3 mmol/L) in patients without diabetes, but the glycemic threshold may shift higher in patients with diabetes who have chronic hyperglycemia and lower in patients with repeated episodes of hypoglycemia associated with intensive diabetes therapy or insulinoma.
¶ Acute diastolic dysfunction from uncontrolled hypertension can cause a hyperadrenergic state and pulmonary edema, while heart failure from dilated cardiomyopathy can develop from many of these etiologies if severe.
Δ Older adults and patients with diabetes may complain of dyspnea alone, or malaise, nausea, epigastric discomfort, palpitations, or syncope.
◊ Clinical manifestations of intoxication are highly variable.
§ For the Hunter criteria, refer to UpToDate content on serotonin toxicity and algorithm on diagnosis of serotonin syndrome.
¥ Diagnosis is apparent if envenomation is witnessed, but the envenomation may not be witnessed.Do you want to add Medilib to your home screen?