HPA-G Complete Profile

Serotonin is synthesised in enterochromaffin cells and central neurons from tryptophan. Peripheral measurements reflect predominantly gut-derived serotonin and renal clearance of metabolites. Central serotonergic tone modulates mood, appetite, sleep initiation, and gastrointestinal motility; dysregulation is implicated in mood disorders, anxiety, and functional gastrointestinal syndromes.

Low urinary serotonin patterns are associated with depressive symptoms, poor sleep quality, and carbohydrate craving. Elevated patterns may accompany carcinoid syndrome or be seen with certain dietary and supplement influences. The result is interpreted within the HPA-G framework as one element of neuroendocrine balance.

Dopamine is a catecholamine neurotransmitter synthesised from tyrosine, governing motivation, reward, motor control, and executive function. Urinary dopamine reflects both adrenal synthesis and renal metabolism of circulating catecholamines; interpretation accounts for peripheral sources and does not directly quantify brain dopaminergic activity.

Low dopamine patterns correlate with diminished motivation, fatigue, attention deficits, and anhedonia. Elevated patterns may reflect stress response, certain medications, or dietary catecholamine precursors. Dopamine is interpreted alongside norepinephrine and the HPA axis in the profile.

Norepinephrine is synthesised from dopamine in sympathetic neurons and the adrenal medulla. It mediates alertness, arousal, attention, and the sympathetic stress response. Urinary norepinephrine captures integrated adrenergic output over the collection window; it does not distinguish central from peripheral sources.

Elevated norepinephrine patterns suggest sympathetic overdrive, chronic stress, or anxiety states; low patterns may indicate fatigue, orthostatic intolerance, or adrenergic depletion. The result is contextualised with epinephrine and cortisol to map stress physiology.

Epinephrine is synthesised in the adrenal medulla from norepinephrine via phenylethanolamine-N-methyltransferase. It mediates acute metabolic and cardiovascular responses to stress. Urinary epinephrine reflects adrenal output and is influenced by sleep, acute stressors, and medications.

Elevated epinephrine patterns are seen with acute or chronic stress, anxiety, and panic; low patterns may accompany adrenal hypofunction or beta-blocker use. Interpretation is integrated with norepinephrine and cortisol to assess hypothalamic–pituitary–adrenal and sympathetic balance.

GABA is the principal inhibitory neurotransmitter in the central nervous system, synthesised from glutamate by glutamic acid decarboxylase. Peripheral GABA measured in urine originates largely from gut microbiota and enterocytes; its relationship to central GABAergic tone is contested and indirect.

Low GABA patterns are theoretically associated with anxiety, insomnia, and heightened stress reactivity, though the validity of peripheral GABA as a proxy for brain function remains debated. Elevated patterns are uncommon and may reflect dietary or microbial sources.

Glutamate is the predominant excitatory neurotransmitter in the brain and a ubiquitous metabolic intermediate. Urinary glutamate reflects renal excretion of amino acids and does not quantify synaptic glutamatergic activity; dietary protein and gut metabolism are major sources.

Elevated glutamate patterns are theoretically linked to excitotoxicity, anxiety, and neuroinflammation in functional neurology models, though peripheral measurement does not establish causality. Low patterns are uncommon. Interpretation is exploratory.

Cortisol is the principal glucocorticoid, synthesised in the adrenal cortex under ACTH control. Urinary free cortisol represents the biologically active, unbound fraction filtered by the kidney and integrates cortisol production over the collection period, smoothing episodic secretion.

Elevated urinary cortisol patterns suggest hypercortisolism, chronic stress, or Cushing syndrome (when very high). Low patterns may indicate adrenal insufficiency, HPA axis suppression, or adaptive down-regulation in chronic stress. The HPA-G profile interprets cortisol alongside neurotransmitters to map neuroendocrine resilience.

Creatinine is a stable metabolite of muscle creatine, excreted at a relatively constant rate. Urinary creatinine is used to normalise spot-urine analyte concentrations, correcting for hydration status and urine flow rate.

Creatinine serves as the denominator for all neurotransmitter and cortisol results in this profile. Very low or very high creatinine values may indicate dilute or concentrated specimens, respectively, prompting recollection if outside acceptable limits.

The HPA-G index is a proprietary weighted composite derived from the pattern of inhibitory (serotonin, GABA), excitatory (dopamine, norepinephrine, epinephrine, glutamate), and adrenal (cortisol) markers. It aims to summarise overall neuroendocrine balance and resilience in a single metric.

The index is used by practitioners to guide personalised nutritional and lifestyle interventions within a functional-medicine framework. It is not a diagnostic score and has not been validated against clinical outcomes in peer-reviewed studies.