Dried Urine LCMS Neurotransmitters and Diurnal Hormones II

Serotonin is synthesised from tryptophan predominantly in enterochromaffin cells of the gut and in brainstem raphe nuclei. Central serotonin modulates mood, sleep initiation, and appetite, while peripheral pools regulate gut motility and platelet function. Urinary serotonin reflects whole-body turnover rather than brain activity; the majority derives from the gut.

Urinary serotonin is used to estimate systemic production and may be elevated in carcinoid tumours. In functional-medicine contexts dried-urine measurement is interpreted as a proxy for central tone, though direct correlation with CNS levels is unproven. Low values may accompany subjective mood and sleep complaints.

Dopamine is a catecholamine synthesised from tyrosine that acts as both a neurotransmitter in reward, motivation, and motor pathways and as a precursor to noradrenaline. Urinary dopamine represents peripheral metabolism, with contributions from sympathetic nerves and the adrenal medulla.

Urinary dopamine may be elevated in phaeochromocytoma. In neuroendocrine panels it is interpreted as a marker of motivation, reward drive, and motor tone, though the relationship between urinary excretion and central function is indirect.

Noradrenaline is synthesised from dopamine in sympathetic nerve terminals and the adrenal medulla. It mediates sympathetic 'fight or flight' responses, raising heart rate, blood pressure, and vigilance. Urinary noradrenaline reflects sympathetic activity and adrenal output.

Elevated urinary noradrenaline can indicate sympathetic overactivity, stress, or catecholamine-secreting tumours. In functional assessments it is read as a stress and vigilance marker; high values may correlate with anxiety or sleep fragmentation.

Adrenaline is synthesised in the adrenal medulla by methylation of noradrenaline. It amplifies acute stress responses, increasing cardiac output, bronchodilation, and hepatic glucose release. Urinary adrenaline reflects adrenal medullary secretion.

Elevated urinary adrenaline accompanies acute stress, phaeochromocytoma, and some medication effects. Functional panels interpret it as an acute-stress marker; chronically elevated values may point to dysregulated sympathoadrenal tone.

Cortisol is the principal glucocorticoid secreted by the adrenal zona fasciculata under ACTH control. Its release follows a diurnal rhythm, peaking in the early morning and declining through the day. Urinary cortisol integrates secretion over the collection interval.

Diurnal dried-urine cortisol captures the rhythm of HPA-axis activity. Loss of the normal decline suggests evening hyperactivity; blunted morning values may reflect HPA hyporesponsiveness. Persistent high output warrants exclusion of Cushing syndrome; low output may accompany adrenal insufficiency.

Cortisone is the inactive 11-keto metabolite of cortisol, interconverted locally by 11β-hydroxysteroid dehydrogenase isoforms. Urinary cortisone reflects both hepatic clearance and peripheral tissue regeneration of cortisol.

The cortisol:cortisone ratio provides insight into local cortisol activation and inactivation. A high ratio may indicate increased tissue regeneration of active cortisol; a low ratio suggests enhanced clearance. Interpreted alongside cortisol to assess HPA-axis tone.

DHEA is an adrenal androgen secreted by the zona reticularis, declining with age. It serves as a precursor to testosterone and oestrogens and may modulate immune and metabolic function. Urinary DHEA reflects integrated adrenal output.

Low DHEA may accompany adrenal insufficiency, chronic stress, or ageing. Functional panels interpret it as an anabolic counter-regulatory hormone, balancing cortisol's catabolic effects. Replacement therapy is sometimes used, though benefits remain debated.

Melatonin is synthesised in the pineal gland from serotonin in response to darkness, orchestrating circadian sleep–wake rhythms. Urinary melatonin or its metabolite 6-sulphatoxymelatonin reflects nocturnal pineal output.

Low overnight melatonin suggests impaired pineal function, circadian misalignment, or excessive light exposure. Functional assessments link blunted melatonin to insomnia, shift work, and ageing. Elevated daytime values are uncommon but may indicate mistimed secretion.

GABA is the principal inhibitory neurotransmitter in the CNS, synthesised from glutamate by glutamic acid decarboxylase. Peripheral GABA is produced in the gut and pancreas; it does not cross the blood–brain barrier.

Urinary GABA reflects peripheral production and gut metabolism, not brain activity. Functional panels interpret low values as correlating with anxiety and poor stress resilience, though direct CNS correlation is unproven. Elevated GABA may be seen with certain gut dysbioses.

Glutamate is the primary excitatory neurotransmitter in the CNS and a key metabolic intermediate. Peripheral glutamate derives from diet and tissue metabolism; it does not readily cross the blood–brain barrier.

Urinary glutamate is an indirect marker; functional panels may interpret elevated values as reflecting excitotoxicity risk or metabolic stress, though the link to CNS excitation is tenuous. Low values are less commonly emphasised.

The cortisol:cortisone ratio reflects the balance between 11β-HSD1 (which regenerates cortisol from cortisone) and 11β-HSD2 (which inactivates cortisol). Tissue-specific isoform expression modulates local glucocorticoid availability.

An elevated ratio suggests increased local cortisol regeneration, potentially amplifying glucocorticoid action in target tissues. A reduced ratio indicates enhanced clearance. The ratio helps contextualise absolute cortisol values and may be altered in metabolic syndrome.