Dried Urine LCMS Neurotransmitters and Diurnal Hormones I

Dopamine is a catecholamine neurotransmitter synthesised from tyrosine via tyrosine hydroxylase and aromatic L-amino-acid decarboxylase. It governs motivation, reward, motor control, and executive function. Peripheral synthesis occurs in the adrenal medulla and sympathetic ganglia, and a small fraction of brain dopamine is metabolised and excreted. Urine dopamine reflects both peripheral turnover and a minor contribution from central nervous system metabolism, with metabolites such as homovanillic acid (HVA) offering an indirect window into dopaminergic activity.

Urine dopamine measurement is used in functional neuropsychiatry to explore motivational deficits, anhedonia, attention and executive dysfunction, and suspected catecholamine imbalances. Marked elevations suggest catecholamine-secreting tumours (phaeochromocytoma, paraganglioma), which require plasma or 24-hour urine fractionated metanephrines for definitive diagnosis. Dried-urine dopamine is interpreted as an exploratory marker, not a diagnostic standard.

Norepinephrine is synthesised from dopamine by dopamine beta-hydroxylase in sympathetic neurons and the adrenal medulla. It is the principal sympathetic postganglionic neurotransmitter, regulating arousal, attention, vigilance, and the cardiovascular stress response. Urine norepinephrine reflects sympathetic nervous system activity and adrenal catecholamine output; its metabolite normetanephrine is preferred for phaeochromocytoma screening.

Urine norepinephrine provides a functional snapshot of sympathetic tone. Chronic elevation is seen in sustained stress, anxiety disorders, and catecholamine-secreting tumours; low levels may accompany autonomic dysfunction or adrenal insufficiency. In functional neurotransmitter testing it is interpreted alongside dopamine and epinephrine to map the stress–arousal–motivation axis.

Epinephrine is synthesised from norepinephrine by phenylethanolamine N-methyltransferase, an enzyme almost exclusively expressed in the adrenal medulla. It amplifies the acute stress response, mobilises glucose and fatty acids, and modulates arousal and memory consolidation. Urine epinephrine reflects adrenomedullary secretion rather than neuronal release, with its metabolite metanephrine used in phaeochromocytoma work-up.

Urine epinephrine is a marker of adrenal-mediated acute stress and can be elevated in anxiety, panic disorder, or catecholamine-secreting tumours. Low values may reflect blunted stress reactivity or autonomic dysfunction. It is read alongside norepinephrine and cortisol in functional stress assessment.

Serotonin (5-hydroxytryptamine) is synthesised from tryptophan by tryptophan hydroxylase and aromatic L-amino-acid decarboxylase. The overwhelming majority of body serotonin is synthesised in enterochromaffin cells of the gut, with a small fraction in the central nervous system, where it regulates mood, sleep, appetite, and gastrointestinal motility. The blood–brain barrier restricts exchange, so urine serotonin predominantly reflects peripheral (enteric) synthesis and is metabolised to 5-hydroxyindoleacetic acid (5-HIAA).

Urine serotonin is used in functional testing to explore mood, sleep, and gastrointestinal complaints, though its predominantly peripheral origin limits direct inference about brain serotonergic activity. Marked elevation raises suspicion for carcinoid tumours, which require plasma or 24-hour urine 5-HIAA for definitive work-up. Functional interpretations must distinguish peripheral from central contributions.

GABA is the principal inhibitory neurotransmitter in the mammalian central nervous system, synthesised from glutamate by glutamic acid decarboxylase. It is also produced peripherally in the enteric nervous system, pancreatic beta cells, and immune cells. GABA does not cross the blood–brain barrier; urine GABA therefore reflects peripheral metabolism, and its relationship to central GABAergic tone is indirect and contested.

Urine GABA is measured in functional neurotransmitter panels to explore anxiety, insomnia, and seizure disorders, but the evidence linking peripheral GABA to central nervous system GABA activity is limited. Interpretation is exploratory; clinical decisions about GABA-related disorders rely on history, neurophysiology, and brain imaging rather than urine assays.

Glutamate is the major excitatory neurotransmitter in the central nervous system and a central node in amino-acid and energy metabolism. It does not cross the blood–brain barrier; urine glutamate reflects systemic amino-acid turnover, dietary intake, and peripheral metabolism rather than brain glutamatergic activity.

Urine glutamate measurement in functional testing is used to infer excitatory–inhibitory neurotransmitter balance, but the disconnect between peripheral and central glutamate pools limits clinical interpretation. Elevated urine glutamate may reflect high dietary intake or altered amino-acid metabolism; low values may accompany nutritional deficiency or impaired synthesis.

Cortisol is the principal glucocorticoid in humans, synthesised in the adrenal zona fasciculata under ACTH control with a diurnal rhythm peaking shortly after waking and declining through the day. Free cortisol is filtered by the kidneys; urine cortisol reflects integrated secretion over the collection interval and is less affected by acute sampling stress than single serum samples.

Diurnal urine cortisol sampling captures the rhythm and total cortisol output. Loss of the normal decline (flattened rhythm) is seen in chronic stress, Cushing syndrome, and some psychiatric disorders. Low output across the day may suggest adrenal insufficiency or HPA-axis dysregulation. Dried-urine multiple-timepoint collections are used in functional-medicine assessment of HPA-axis rhythm, though diagnostic endocrinology relies on 24-hour urine free cortisol, saliva, or serum for Cushing or Addison screening.

Cortisone is the inactive 11-keto metabolite of cortisol, interconverted by 11-beta-hydroxysteroid dehydrogenase isoenzymes. It is produced locally in tissues to buffer cortisol activity and is reconverted to cortisol in target tissues. Urine cortisone reflects both adrenal secretion and peripheral cortisol metabolism.

Measuring both cortisol and cortisone in urine provides insight into 11-beta-HSD activity and the balance between active and inactive glucocorticoid forms. Altered cortisol-to-cortisone ratios may reflect enzyme deficiency or altered local tissue glucocorticoid metabolism. This is an emerging functional biomarker; standard clinical practice measures cortisol alone.

Melatonin is synthesised from serotonin in the pineal gland, with secretion peaking at night under the control of the suprachiasmatic nucleus and inhibited by light. It governs circadian rhythm, sleep onset, and antioxidant defences. Melatonin is rapidly metabolised in the liver to 6-hydroxymelatonin sulfate (6-sulfatoxymelatonin, aMT6s), the major urine metabolite, which is often measured as a surrogate for melatonin secretion.

Urine melatonin (or aMT6s) reflects pineal melatonin production and circadian rhythm integrity. Low or shifted peaks are seen in circadian rhythm disorders, jet lag, shift work, and sleep-onset insomnia. The test is used in functional sleep and circadian assessments; clinical sleep medicine typically relies on history, actigraphy, and polysomnography rather than biochemical melatonin measurement.