02 - 2. Laboratory assessment of physical factors

2. Laboratory assessment of physical factors

© SPMM Course 2. Laboratory assessment of physical factors Depression Depression is a clinical diagnosis. A physical examination is always required to rule out several common medical disorders that can present with depression (especially endocrine disorders). Laboratory tests are required if medical causes are suspected and to assess baseline fitness before starting antidepressants. Several chronic medical disorders are associated with depression (e.g. Coronary artery disease, Diabetes mellitus, End-stage renal disease, HIV infection, various malignancies, degenerative neurological disorders and stroke) but these do not ‘present’ with depressive features and as such for a patient presenting with depression, there is no need to exclude all of these medical disorders before diagnosis depression. TEST WHY DO WE DO IT? Full blood count Rule out infectious and inflammatory pathology Thyroid-stimulating hormone (TSH) Rule out hypothyroidism Vitamin B-12 Deficiency can mimic depression HIV test & Syphilis (rapid plasma reagin) In suspected cases of sexually transmitted infections Electrolytes, including calcium, phosphate, and magnesium levels Deficiency can contribute to fatigue and mimic depression GFR and creatinine In preparation for antidepressant use and to rule out renal insufficiency contributing to depression Liver function tests (LFTs) In preparation for antidepressant use and to rule out alcohol-related liver damage in suspected cases Blood and urine toxicology screen In suspected cases of drug abuse 24-hour urinary free cortisol In suspected cases of Cushing disease; will require additional confirmation, as this can be positive in a large number of patients with depression. ACTH stimulation test Addison’s disease can also mimic depression

The following table displays some common abnormalities. Please note that none of the tests below are required routinely during a workup for depression. LAB ABNORMALITIES INTERPRETATION Dexamethasone Suppression Test DST nonsuppression (DST-positive result) is seen in many disorders associated with depression e.g. grief reactions (10%), dysthymic disorders (23%), major depressive disorder (44%), melancholia/somatic syndrome (50%), psychotic affective disorders (69%), and in depression with serious suicidality (78%). DST-positive patients respond more favorably to biological interventions. DST nonsuppression is nonspecific; can be seen in chronic pain, patients with anorexia or bulimia, alcoholism, obsessive-compulsive disorder, or anxiety disorders. Corticotropin-Releasing Hormone Test HPA axis abnormality in major depression results in blunted ACTH response to CRH.

© SPMM Course Serum Thyroxine Concentrations 1% and 4% of depressed patients, esp. women show evidence of overt hypothyroidism; 4% to 40% have subclinical hypothyroidism, contributing to treatment failure. Serum T4 reductions may accompany treatment with antidepressants, lithium, sleep deprivation, or ECT, especially in responders. Thyrotropin-Releasing Hormone Test ~ 30% of depressed patients show blunted TSH response during depression

Anxiety and other neuroses A number of medical disorders can directly contribute to anxiety and panic attacks, but in practice, patients seeking clinical consultations seldom require specific investigations to diagnose these conditions. Diagnostic possibilities for panic attacks include paroxysmal atrial tachycardia, pulmonary embolus, seizure disorder, Meniere's disease, transient ischemic attack, carcinoid syndrome, Cushing's disease, hyperthyroidism, hypoglycemia, and pheochromocytoma. A physical examination is warranted for all first presentations; extensive medical evaluation for these disorders is indicated only when other features suggest physical disease. Lactate infusion: Nearly 72% patients with panic disorder have a panic attack when administered IV injections of sodium lactate. Therefore, lactate provocation is used to confirm a diagnosis of panic disorder. Hyperventilation and CO2 inhalation have been used. Panic attacks triggered by sodium lactate are not inhibited by peripherally acting beta-blockers but are inhibited by benzodiazepines and tricyclic drugs. Narcoanalysis: Interviews with amobarbital are very rarely used in current clinical practice for diagnostic and therapeutic indications. These are sometimes helpful in differentiating nonorganic and organic conditions, particularly in patients with symptoms of catatonia, stupor, and muteness. Organic conditions tend to worsen with infusions of amobarbital, but nonorganic or psychogenic conditions tend to get better because of disinhibition, decreased anxiety, or increased relaxation. Therapeutically, amobarbital interviews are useful in disorders of repression and dissociation such as amnesia and fugue. Benzodiazepines can be substituted for amobarbital. Psychosis Differential diagnoses to be considered in the history of presenting illness: head trauma (subdural haematoma), seizures, new-onset headaches, focal neurological deficits, abnormal body movements, memory loss, and tremor especially in older patients, recreational drug use, dietary history (deficiencies of vitamin B12, folate, thiamine, and niacin can all cause psychosis). Physical examination: vital signs, level of consciousness, evidence of malnutrition, signs of hypoor hyperthyroidism or cushingoid features, rashes associated with autoimmune disorders,

© SPMM Course dysmorphic facial features (genetic syndromes e.g velocardiofacial), focal neurological signs and examination for signs of raised intracranial pressure Initial tests TESTS WHY DO WE DO IT? Full blood count Rule out infectious and inflammatory pathology; the baseline for starting haemotoxic antipsychotics such as olanzapine, clozapine. Thyroid profile (TSH, free T4) Rule out hypo or hyperthyroidism. If abnormal carry out free T3 level and thyroid autoantibodies ELISA for anti-thyroid peroxidase Blood glucose, lipid profile, ECG Baseline for antipsychotic therapy; metabolic syndrome is common among patients with psychotic disorders Prolactin levels Baseline for antipsychotic therapy

In suspected cases of sexually transmitted infections Electrolytes, including calcium, phosphate, and magnesium levels May be abnormal if there is an underlying metabolic or endocrine disturbance GFR and creatinine In preparation for antidepressant use and to rule out renal insufficiency contributing to depression Liver function tests (LFTs) In preparation for antipsychotic use; to rule out chronic alcohol abuse and Wilson's disease in suspected cases Blood and urine toxicology screen Acute toxic drug effects the most common cause of psychosis; screen for amphetamines, cocaine, cannabis, and benzodiazepines

SUSPECTED CONDITION TESTS REQUIRED Delirium with psychosis Blood glucose, Blood alcohol, Urine microscopy and culture, Blood culture, Chest X-ray. Suspected STDs HIV test & Syphilis (rapid plasma reagin) Screen for autoimmune disorders in suspected cases Anti-Nuclear Antibodies, CRP and ESR Suspected encephalitis syndrome NMDA receptor (NMDAR) and voltage-gated potassium channel receptor (VGKC) auto-antibodies (IgG) Cushing's syndrome 24-hour urinary free cortisol test followed by DST and ACTH challenge, evening salivary cortisol, and the dexamethasone-corticotropin-releasing hormone test Porphyria Spot urine sample for porphobilinogen during acute attack, and 24-hour urine for porphyrins, porphobilinogen, and delta-aminolevulinic acid Hyperparathyroidism Serum calcium and serum parathyroid hormone test Wilson's disease Serum ceruloplasmin, 24-h copper excretion test Lysosomal storage diseases Skin biopsy, genetic tests, and the detection of serum alpha-galactosidase enzyme Homocystinuria Homocysteine in urine and blood and molecular genetic testing Metachromatic leukodystrophy Arylsulfatase A enzyme activity in WBCs or in cultured skin fibroblasts Malnourishment Serum homocysteine and foalte (folate deficiency) , vitamin B12, niacin, tryptophan, nicotinamide adenine dinucleotide (NAD) and NADP CNS lesions MRI or CT scan; EEG if TLE is suspected

Porphyrias: Acute intermittent porphyria (AIP) is one of the groups of disorders of haem

© SPMM Course metabolism, characterised by neurological and psychiatric manifestations without obvious cutaneous markers. AIP manifests itself by abdomen pain, neuropathies, and constipation, but, unlike most types of porphyria, patients with AIP do not have a rash. It is an autosomal dominant disorder with the presentation starting between ages 18 and 40. It is episodic in nature, and the episodes are often triggered by certain medications including estrogens, barbiturates and benzodiazepines. Diclofenac can precipitate an episode. Psychiatric manifestations include depression, anxiety, delirium and psychosis. Most important lab test is demonstrating increased urinary porphobilinogen during acute attacks. Treatment is aimed at reducing haem synthesis by administering haemin. Autoimmune encephalitis presenting as psychosis: Autoimmune disorders with antibodies produced against crucial neurotransmitter receptors can present with psychosis. Several anecdotal reports have pinpointed the following receptors as most vulnerable in this regard.  Voltage Gated Potassium Channel complex (LGI1, CASPR2, contactin-2)  N-Methyl-D-aspartate receptor (NMDA)  AMPA receptor  GABA-B  Glycine receptor Some studies have estimated that 6.3% of first onset psychosis patients have pathogenic antibodies against brain receptors (Zandi et al., 2011). The most well known of these syndromes is the anti-NMDA receptor (NMDAR) encephalitis.  Anti-NMDAR antibodies result in the titre-dependent destruction of synaptic NMDAR through crosslinking and internalisation.  Around 4% of patients with anti-NMDAR present with isolated psychiatric symptoms.  It is more common in females (80%) than males  ~50% of women with anti-NMDAR have an underlying ovarian teratoma.  75% of patients first present to a psychiatrist with acute psychosis and/or mania.  Psychosis associated with anti-NMDAR encephalitis usually presents with a prodromal illness (fever, headaches, malaise). In suspected cases, the following investigations are appropriate o Serum NMDAR and VGKC antibodies o Test for ANA, CRP, ESR, FBC, U+E (low sodium is seen in those with anti-VGKC antibodies) o If there is a strong suspicion EEG (look for encephalopathy with disorganized

© SPMM Course delta/theta activity) and MRI brain (look for medial temporal hyperintensity, usually seen in T2 or FLAIR sequences in the hippocampi, frontobasal and insular regions and basal ganglia; normal in ~50%). o Confirmatory diagnosis requires CSF analysis: Lymphocytic pleocytosis, elevated protein and oligoclonal bands are seen in ~60% of cases; almost all have intrathecal anti-NMDAR antibodies. Note that patients who are cured of anti-NMDAR encephalitis may continue having detectable antibodies in serum and/or CSF. CSF antibodies rise during each relapse o Elevated creatine kinase is a non-specific feature of the anti-NMDAR illness. o In females with anti-NMDAR, ask for ultrasound or CT pelvis. Anti-NMDAR encephalitis usually responds to 3 days of methylprednisolone orally or intravenous followed by oral prednisolone, in association with 5 days of plasma exchange. The remission thus achieved can be maintained by either (1) steroids alone; (2) steroids with a steroid-sparing agent, such as azathioprine or mycophenolate mofetil or (3) rituximab. Regular benzodiazepines may be required. AVOID ANTIPSYCHOTICS as dystonic reactions and NMS-like syndrome with rigidity, hyperthermia, and autonomic instability might occur on the use of antipsychotics in patients with anti-NMDAR antibodies. Dementia Patients presenting with memory difficulties always require a thorough physical examination to look for signs of neurological disorders. In addition, several nutritional and metabolic factors can produce what is called ‘reversible’ dementia – cognitive impairment with no progressive, degenerative pathology. Laboratory investigations required for initial dementia workup are shown below. TEST WHY DO WE DO IT? Full blood count Rule out infectious and inflammatory pathology; the baseline for starting antidementia medications. Thyroid profile (TSH, free T4) Low T4 can cause cognitive impairment Blood glucose, lipid profile, ECG Baseline before starting antidementia medications; metabolic syndrome is common among patients with vascular dementia Thiamine, folate levels Thiamine deficiency can result in memory impairment esp. in alcoholics Tests for syphilis or HIV HIV is associated with cognitive impairment that can worsen with opportunistic infections. Electrolytes, including calcium, phosphate, and magnesium levels May be abnormal if there is an underlying metabolic or endocrine disturbance causing cognitive impairment GFR and creatinine In preparation for antidementia medications Liver function tests (LFTs) In preparation for antidementia medications CT or MRI brain This is becoming a routine practice though the diagnostic yield of routine imaging is low in senile dementia of Alzheimer’s type. Recommended when suspecting vascular dementia, subdural hematoma or tumours.