Several thyroid function tests are available, including tests for thyroxine (T₄) by competitive protein binding (T₄D) and by radioimmunoassay (T₄RIA) involving a specific antigen-antibody reaction. More than 90 percent of T₄ is bound to serum protein and is responsible for thyroid-stimulating hormone (TSH) secretion and cellular metabolism. Other thyroid measures include the free T₄ index (FT₄I), triiodothyronine uptake, and total serum triiodothyronine measured by radioimmunoassay (T₃RIA). These tests are used to rule out hypothyroidism, which can appear with symptoms of depression. In some studies, up to 10 percent of patients complaining of depression and associated fatigue had incipient hypothyroid disease. Other associated signs and symptoms common to both depression and hypothyroidism include weakness, stiffness, poor appetite, constipation, menstrual irregularities, slowed speech, apathy, impaired memory, and even hallucinations and delusions. Lithium can cause hypothyroidism and, more rarely, hyperthyroidism. Neonatal hypothyroidism results in mental retardation and is preventable if the diagnosis is made at birth.

The thyrotropin-releasing hormone (TRH) stimulation test is indicated for patients whose marginally abnormal thyroid test results suggest subclinical hypothyroidism, which can account for clinical depression. The test is also used for patients with possible lithium-induced hypothyroidism. The procedure entails an intravenous (IV) injection of 500 mg of TRH, which produces a sharp rise in serum TSH when measured at 15, 30, 60, and 90 minutes. An increase in serum TSH from 5 to 25 IU/mL above baseline is normal. An increase of less than 7 IU/mL is considered a blunted response, which may correlate with a diagnosis of a depressive disorder. Eight percent of all patients with depressive disorders have some thyroid illness.

The dexamethasone-suppression test (DST) is used to help confirm a diagnostic impression of major depressive disorder.

The patient is given 1 mg of dexamethasone (a long-acting synthetic glucocorticoid) by mouth at 11 pm, and the plasma cortisol level is measured at 8 am, 4 pm, and 11 pm. Plasma cortisol concentrations above 5 mg/dL (known as nonsuppression) are considered abnormal (i.e., a positive result). Suppression of cortisol indicates that the hypothalamic-adrenal-pituitary axis is functioning properly. Since the 1930s, dysfunction of this axis has been known to be associated with stress.

The problems associated with the DST include varying reports of sensitivity and specificity. False-positive and false-negative results are common, and many medical conditions and pharmacological agents can interfere with results. Some evidence indicates that patients with a positive DST result
(especially 10 mg/dL) will have a good response to somatic treatment, such as electroconvulsive therapy (ECT) or cyclic antidepressant therapy.

Many other hormones affect behavior. Exogenous hormonal administration has been shown to affect behavior, and known endocrine diseases have associated mental disorders. In addition to thyroid hormones, these hormones include the anterior pituitary hormone prolactin, growth hormone, somatostatin, gonadotropin-releasing hormone (GnRH), the sex steroids, luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and estrogen. Melatonin from the pineal gland has been implicated in seasonal affective disorder. Symptoms of anxiety or depression in some patients may be explained on the basis of unspecified changes in endocrine function or homeostasis.

The level of serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) is elevated in the urine of patients with carcinoid tumors. Elevated levels are noted at times in patients who take phenothiazine medication and in those who eat foods high in serotonin (e.g., walnuts, bananas, and avocados). The concentration of 5-HIAA in cerebrospinal fluid is low in some persons who are in a suicidal depression and in postmortem studies of those who have committed suicide in particularly violent ways. Low 5-HIAA levels in cerebrospinal fluid are associated with violence in general. Norepinephrine and its metabolic products—metanephrine, normetanephrine, and vanillylmandelic acid (VMA)—can be measured in urine, blood, and plasma. Plasma catecholamine levels are markedly elevated in pheochromocytoma, which is associated with anxiety, agitation, and hypertension. Some patients with chronic anxiety may exhibit elevated blood norepinephrine and epinephrine levels. Some depressed patients have a low urinary norepinephrine-to-epinephrine ratio (NE : E).

High levels of urinary norepinephrine and epinephrine have been found in some patients with posttraumatic stress disorder. The norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) concentration is decreased in patients with severe depressive disorders, especially those patients who attempt suicide.

Creatinine clearance detects early kidney damage and can be serially monitored to follow the course of renal disease. Blood urea nitrogen (BUN) is also elevated in renal disease and is excreted via the kidneys; serum BUN and creatinine levels are monitored in patients taking lithium. If the serum BUN or creatinine level is abnormal, the patient’s 2-hour creatinine clearance and ultimately the 24-hour creatinine clearance are tested.