Precipitation of uric acid crystals, and conversely their dissolution, is known to be dependent on the concentration of uric acid in solution, pH, sodium concentration, and temperature. Established treatments address these parameters.

Low temperature is a commonly reported trigger of acute gout: an example would be a day spent standing in cold water, followed by an attack of gout the next morning. This is believed to be due to temperature-dependent precipitation of uric acid crystals in tissues at below normal temperature. Thus, one aim of prevention is to keep the hands and feet warm, and soaking in hot water may be therapeutic.

Idiopathic hypouricemia usually requires no treatment. In some cases, hypouricemia is a medical sign of an underlying condition that does require treatment. For example, if hypouricemia reflects high excretion of uric acid into the urine (hyperuricosuria) with its risk of uric acid nephrolithiasis, the hyperuricosuria may require treatment.

Although normally benign, idiopathic renal hypouricemia may increase the risk of exercise-induced acute renal failure.

Patients at risk for acute uric acid nephropathy can be given allopurinol or rasburicase (a recombinant urate oxidase) prior to treatment with cytotoxic drugs.

In 2011, Howard proposed a refinement of the standard Cairo-Bishop definition of TLS accounting for 2 limitations:

- Two or more electrolyte laboratory abnormalities must be present simultaneously to be considered related to TLS. In fact, some patients may present with one abnormality, but later another one may develop that is unrelated to the TLS (e.g., hypocalcemia associated with sepsis).

- A 25% change from baseline should not be considered a criterion since such increases are rarely clinically important unless the value is already outside the normal range.

Moreover, any symptomatic hypocalcemia should constitute clinical TLS.

Hyperuricemia is a classic feature of gout, but nearly half of the time gout occurs without hyperuricemia and most people with raised uric acid levels never develop gout. Thus, the diagnostic utility of measuring uric acid levels is limited. Hyperuricemia is defined as a plasma urate level greater than 420 μmol/l (7.0 mg/dl) in males and 360 μmol/l (6.0 mg/dl) in females. Other blood tests commonly performed are white blood cell count, electrolytes, kidney function and erythrocyte sedimentation rate (ESR). However, both the white blood cells and ESR may be elevated due to gout in the absence of infection. A white blood cell count as high as 40.0×10/l (40,000/mm) has been documented.

Gout may be diagnosed and treated without further investigations in someone with hyperuricemia and the classic acute arthritis of the base of the great toe (known as podagra). Synovial fluid analysis should be done, however, if the diagnosis is in doubt. X-rays, while useful for identifying chronic gout, have little utility in acute attacks.

People about to receive chemotherapy for a cancer with a high cell turnover rate, especially lymphomas and leukemias, should receive prophylactic oral or IV allopurinol (a xanthine oxidase inhibitor, which inhibits uric acid production) as well as adequate IV hydration to maintain high urine output (> 2.5 L/day). Allopurinol mechanically blocks rasburicase's operation to solubilize.

Rasburicase is an alternative to allopurinol and is reserved for people who are high-risk in developing TLS. It is a synthetic urate oxidase enzyme and acts by degrading uric acid. However, it's not clear if it results in any important benefits as of 2014.

Alkalization of the urine with acetazolamide or sodium bicarbonate is controversial. Routine alkalization of urine above pH of 7.0 is not recommended. Alkalization is also not required if uricase is used.

Treatment is focused on preventing deposition of uric acid within the urinary system by increasing urine volume with potent diuretics such as furosemide. Raising the urinary pH to a level higher than 7 (alkalinization) is often difficult to attain, although sodium bicarbonate and/or acetazolamide are sometimes used in an attempt to increase uric acid solubility.

Dialysis (preferably hemodialysis) is started if the above measures fail.

In people with a history of stones, those who are less than 50 years of age and are presenting with the symptoms of stones without any concerning signs do not require helical CT scan imaging. A CT scan is also not typically recommended in children.

Otherwise a noncontrast helical CT scan with sections is the diagnostic modality of choice in the radiographic evaluation of suspected nephrolithiasis. All stones are detectable on CT scans except very rare stones composed of certain drug residues in the urine, such as from indinavir. Calcium-containing stones are relatively radiodense, and they can often be detected by a traditional radiograph of the abdomen that includes the kidneys, ureters, and bladder (KUB film). Some 60% of all renal stones are radiopaque. In general, calcium phosphate stones have the greatest density, followed by calcium oxalate and magnesium ammonium phosphate stones. Cystine calculi are only faintly radiodense, while uric acid stones are usually entirely radiolucent.

Where a CT scan is unavailable, an intravenous pyelogram may be performed to help confirm the diagnosis of urolithiasis. This involves intravenous injection of a contrast agent followed by a KUB film. Uroliths present in the kidneys, ureters or bladder may be better defined by the use of this contrast agent. Stones can also be detected by a retrograde pyelogram, where a similar contrast agent is injected directly into the distal ostium of the ureter (where the ureter terminates as it enters the bladder).

Renal ultrasonography can sometimes be useful, as it gives details about the presence of hydronephrosis, suggesting the stone is blocking the outflow of urine. Radiolucent stones, which do not appear on KUB, may show up on ultrasound imaging studies. Other advantages of renal ultrasonography include its low cost and absence of radiation exposure. Ultrasound imaging is useful for detecting stones in situations where X-rays or CT scans are discouraged, such as in children or pregnant women. Despite these advantages, renal ultrasonography in 2009 was not considered a substitute for noncontrast helical CT scan in the initial diagnostic evaluation of urolithiasis. The main reason for this is that compared with CT, renal ultrasonography more often fails to detect small stones (especially ureteral stones), as well as other serious disorders that could be causing the symptoms. A 2014 study confirmed that ultrasonography rather than CT as an initial diagnostic test results in less radiation exposure and did not find any significant complications.

Laboratory investigations typically carried out include:

- microscopic examination of the urine, which may show red blood cells, bacteria, leukocytes, urinary casts and crystals;

- urine culture to identify any infecting organisms present in the urinary tract and sensitivity to determine the susceptibility of these organisms to specific antibiotics;

- complete blood count, looking for neutrophilia (increased neutrophil granulocyte count) suggestive of bacterial infection, as seen in the setting of struvite stones;

- renal function tests to look for abnormally high blood calcium blood levels (hypercalcemia);

- 24 hour urine collection to measure total daily urinary volume, magnesium, sodium, uric acid, calcium, citrate, oxalate and phosphate;

- collection of stones (by urinating through a StoneScreen kidney stone collection cup or a simple tea strainer) is useful. Chemical analysis of collected stones can establish their composition, which in turn can help to guide future preventive and therapeutic management.

Although this hypothesis is well known among clinicians and individuals with diabetes, there is little scientific evidence to support it. Clinical studies indicate that a high fasting glucose in the morning is more likely because the insulin given on the previous evening fails to last long enough. Studies from 2007 onwards using continuous glucose monitoring show that a high glucose in the morning is not preceded by a low glucose during the night. Furthermore, many individuals with hypoglycemic episodes during the night don't wake due to a failure of release of epinephrine during nocturnal hypoglycemia. Thus, Somogyi's theory is not assured and may be refuted.

In theory, avoidance is simply a matter of preventing hyperinsulinemia. In practice, the difficulty for a diabetic person to aggressively dose insulin to keep blood sugars levels close to normal and at the same time constantly adjust the insulin regimen to the dynamic demands of exercise, stress, and wellness can practically assure occasional hyperinsulinemia. The pharmacokinetic imperfections of all insulin replacement regimens is a severe limitation.

Some practical behaviors which are useful in avoiding chronic Somogyi rebound are:

- frequent blood glucose monitoring (8–10 times daily);

- continuous blood glucose monitoring;

- logging and review of blood glucose values, searching for patterns of low blood sugar values;

- conservative increases in insulin delivery;

- awareness to the signs of hypoglycemia;

- awareness to hyperglycemia in response to increased delivery of insulin;

- use of appropriate types of insulin (long-acting, short-acting, etc.) in appropriate amounts.

The urate to creatinine (breakdown product of creatine phosphate in muscle) concentration ratio in urine is elevated. This is a good indicator of acid overproduction. For children under ten years of age with LNS, a urate to creatinine ratio above two is typically found. Twenty-four-hour urate excretion of more than 20 mg/kg is also typical but is not diagnostic. Hyperuricemia (serum uric acid concentration of >8 mg/dL) is often present but not reliable enough for diagnosis. Activity of the HGPRT enzyme in cells from any type of tissue (e.g., blood, cultured fibroblasts, or lymphoblasts) that is less than 1.5% of normal enzyme activity confirms the diagnosis of Lesch–Nyhan syndrome. Molecular genetic studies of the HPRT gene mutations may confirm diagnosis, and are particularly helpful for subsequent 'carrier testing' in at-risk females such as close family relatives on the female side.

A tophus (Latin: "stone", plural tophi) is a deposit of uric acid crystals, in the form of monosodium urate crystals, in people with longstanding hyperuricemia (high levels of uric acid in the blood). Tophi are pathognomonic for the disease gout. Most people with tophi have had previous attacks of acute arthritis, eventually leading to the formation of tophi. Chronic tophaceous gout is known as Harrison Syndrome.

Tophi form in the joints, cartilage, bones, and other places throughout the body. Sometimes, tophi break through the skin and appear as white or yellowish-white, chalky nodules. Without treatment, tophi may develop on average about ten years after the onset of gout, although their first appearance can range from three to forty-two years. The development of gouty tophi can also limit joint function and cause bone destruction, leading to noticeable disabilities, especially when gout cannot successfully be treated. When uric acid levels and gout symptoms cannot be controlled with standard gout medicines that decrease the production of uric acid (e.g., allopurinol, febuxostat) or increase uric acid elimination from the body through the kidneys (e.g., probenecid), this can be referred to as refractory chronic gout (RCG). They are more apt to appear early in the course of the disease in people who are older.

Although less common, tophi can also form in the kidneys and nasal cartilage.

The use of biochemical testing for the detection of carriers is technically demanding and not often used. Biochemical analyses that have been performed on hair bulbs from at risk women have had a small number of both false positive and false negative outcomes. If only a suspected carrier female is available for mutation testing, it may be appropriate to grow her lymphocytes in 6-thioguanine (a purine analogue), which allows only HGPRT-deficient cells to survive. A mutant frequency of 0.5–5.0 × 10 is found in carrier females, while a non-carrier female has a frequency of 1–20 × 10. This frequency is usually diagnostic by itself.

Molecular genetic testing is the most effective method of testing, as HPRT1 is the only gene known to be associated with LNS. Individuals who display the full Lesch–Nyhan phenotype all have mutations in the HPRT1 gene. Sequence analysis of mRNA is available clinically and can be utilized in order to detect HPRT1 mutations in males affected with Lesch–Nyhan syndrome. Techniques such as RT-PCR, multiplex genomic PCR, and sequence analysis (cDNA and genomic DNA), used for the diagnosis of genetic diseases, are performed on a research basis. If RT-PCR tests result in cDNA showing the absence of an entire exon or exons, then multiplex genomic PCR testing is performed. Multiplex genomic PCR testing amplifies the nine exons of the HPRT1 gene as eight PCR products. If the exon in question is deleted, the corresponding band will be missing from the multiplex PCR. However, if the exon is present, the exon is sequenced to identify the mutation, therefore causing exclusion of the exon from cDNA. If no cDNA is created by RT-PCR, then multiplex PCR is performed on the notion that most or all of the gene is obliterated.

The current reference range for acceptable blood lead concentrations in healthy persons without excessive exposure to environmental sources of lead is less than 5 µg/dL for children. It was less than 25 µg/dL for adults. Previous to 2012 the value for children was 10 (µg/dl). The current biological exposure index (a level that should not be exceeded) for lead-exposed workers in the U.S. is 30 µg/dL in a random blood specimen.

In 2015, US HHS/CDC/NIOSH designated 5 µg/dL (five micrograms per deciliter) of whole blood, in a venous blood sample, as the reference blood lead level for adults. An elevated BLL is defined as a BLL ≥5 µg/dL. This case definition is used by the ABLES program, the Council of State and Territorial Epidemiologists (CSTE), and CDC’s National Notifiable Diseases Surveillance System (NNDSS). Previously (i.e. from 2009 until November 2015), the case definition for an elevated BLL was a BLL ≥10 µg/dL. The U.S. national BLL geometric mean among adults was 1.2 μg/dL in 2009–2010.

Blood lead concentrations in poisoning victims have ranged from 30->80 µg/dL in children exposed to lead paint in older houses, 77–104 µg/dL in persons working with pottery glazes, 90–137 µg/dL in individuals consuming contaminated herbal medicines, 109–139 µg/dL in indoor shooting range instructors and as high as 330 µg/dL in those drinking fruit juices from glazed earthenware containers.

Two elements are considered: radiology and joint fluid analysis.

Radiology has a large role to play in finding chondrocalcinosis, with radiographs, CT scans, MRIs, US, and nuclear medicine all having a part. CT scans and MRIs show calcific masses (usually within the ligamentum flavum or joint capsule), however radiography is more successful. At ultrasound, chondrocalcinosis may be depicted as echogenic foci with no acoustic shadow within the hyaline cartilage. As with most conditions, CPPD can present with similarity to other diseases such as ankylosing spondylitis and gout.

Arthrocentesis, or removing synovial fluid from the affected joint, is performed to test the synovial fluid for the calcium pyrophosphate crystals that are present in CPPD. When stained with H&E stain, calcium pyrophosphate crystals appears deeply blue ("basophilic"). However, CPP crystals are much better known for their rhomboid shape and weak positive birefringence on polarized light microscopy, and this method remains the most reliable method of identifying the crystals under the microscope. However, even this method suffers from poor sensitivity, specificity, and inter-operator agreement.

These two modalities currently define CPPD disease but lack diagnostic accuracy, and are potentially epiphenomenological.

In people aged 18 years or older hypertension is defined as a systolic or a diastolic blood pressure measurement consistently higher than an accepted normal value (this is above 129 or 139 mmHg systolic, 89 mmHg diastolic depending on the guideline). Other thresholds are used (135 mmHg systolic or 85 mmHg diastolic) if measurements are derived from 24-hour ambulatory or home monitoring. Recent international hypertension guidelines have also created categories below the hypertensive range to indicate a continuum of risk with higher blood pressures in the normal range. The "Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure" (JNC7) published in 2003 uses the term prehypertension for blood pressure in the range 120–139 mmHg systolic or 80–89 mmHg diastolic, while European Society of Hypertension Guidelines (2007) and British Hypertension Society (BHS) IV (2004) use optimal, normal and high normal categories to subdivide pressures below 140 mmHg systolic and 90 mmHg diastolic. Hypertension is also sub-classified: JNC7 distinguishes hypertension stage I, hypertension stage II, and isolated systolic hypertension. Isolated systolic hypertension refers to elevated systolic pressure with normal diastolic pressure and is common in the elderly. The ESH-ESC Guidelines (2007) The results also demonstrated a correlation of chronically low vitamin D levels with a higher chance of becoming hypertensive. Supplementation with vitamin D over 18 months in normotensive individuals with vitamin D deficiency did not significantly affect blood pressure.

There are no laboratory tests used to diagnose RVT.

Observing the patient's symptoms, medical history and imaging remain the fundamental source for diagnosing RVT. Imaging is used to detect the presence of a blood clot. In an abnormal kidney with RVT, a blood clot is present in the renal vein. In cases where the renal vein is suddenly and/or fully blocked, the kidneys will enlarge, reaching its maximum size within a week. An ultrasound imaging can be used to observe and track the size of the kidneys in RVT patients. Ultrasound is not efficient for use in detecting blood flow in the renal veins and artery. Instead a color doppler ultrasound may be used to detect renal blood flow. It is most commonly used to detect RVT in patients who have undergone renal transplantation. CT angiography is currently the top choice in diagnosing RVT. It is non-invasive, relatively cheap and fast with high accuracy. CT scanning can be used to detect renal enlargement, renal tumors, blood flow and other renal pathologies. An alternative is magnetic resonance angiography or MRA. It is non-invasive, fast and avoids radiation (unlike a CT scan) but it is relatively expensive. MRA produces detailed images of the renal blood flow, vesicle walls, the kidneys and any surrounding tissue. An inferior venocavography with selective venography can be used to rule out the diagnoses of RVT.

For most patients, health care providers diagnose high blood pressure when blood pressure readings are consistently 140/90 mmHg or above. A blood pressure test can be done in a health care provider’s office or clinic. To track blood pressure readings over a period of time, the health care provider may ask the patient to come into the office on different days and at different times. The health care provider also may ask the patient to check readings at home or at other locations that have blood pressure equipment and to keep a written log of results. The health care provider usually takes 2–3 readings at several medical appointments to diagnose high blood pressure. Using the results of the blood pressure test, the health care provider will diagnose prehypertension or high blood pressure if:

- For an adult, systolic or diastolic readings are consistently higher than 120/80 mmHg.

- A child’s blood pressure numbers are outside average numbers for children of the same age, gender, and height.

Once the health care provider determines the severity, he or she can order additional tests to determine if the blood pressure is due to other conditions or medicines or if there is primary high blood pressure. Health care providers can use this information to develop a treatment plan.

Hypertension is diagnosed on the basis of a persistently high resting blood pressure. Traditionally, the National Institute of Clinical Excellence recommends three separate resting sphygmomanometer measurements at monthly intervals. The American Heart Association recommends at least three resting measurements on at least two separate health care visits.

For an accurate diagnosis of hypertension to be made, it is essential for proper blood pressure measurement technique to be used. Improper measurement of blood pressure is common and can change the blood pressure reading by up to 10 mmHg, which can lead to misdiagnosis and misclassification of hypertension. Correct blood pressure measurement technique involves several steps. Proper blood pressure measurement requires the person whose blood pressure is being measured to sit quietly for at least five minutes which is then followed by application of a properly fitted blood pressure cuff to a bare upper arm. The person should be seated with their back supported, feet flat on the floor, and with their legs uncrossed. The person whose blood pressure is being measured should avoid talking or moving during this process. The arm being measured should be supported on a flat surface at the level of the heart. Blood pressure measurement should be done in a quiet room so the medical professional checking the blood pressure can hear the Korotkoff sounds while listening to the brachial artery with a stethoscope for accurate blood pressure measurements. The blood pressure cuff should be deflated slowly (2-3 mmHg per second) while listening for the Korotkoff sounds. The bladder should be emptied before a person's blood pressure is measured since this can increase blood pressure by up to 15/10 mmHg. Multiple blood pressure readings (at least two) spaced 1-2 minutes apart should be obtained to ensure accuracy. Ambulatory blood pressure monitoring over 12 to 24 hours is the most accurate method to confirm the diagnosis.

An exception to this is those with very high blood pressure readings especially when there is poor organ function. Initial assessment of the hypertensive people should include a complete history and physical examination. With the availability of 24-hour ambulatory blood pressure monitors and home blood pressure machines, the importance of not wrongly diagnosing those who have white coat hypertension has led to a change in protocols. In the United Kingdom, current best practice is to follow up a single raised clinic reading with ambulatory measurement, or less ideally with home blood pressure monitoring over the course of 7 days. The United States Preventative Services Task Force also recommends getting measurements outside of the healthcare environment. Pseudohypertension in the elderly or noncompressibility artery syndrome may also require consideration. This condition is believed to be due to calcification of the arteries resulting in abnormally high blood pressure readings with a blood pressure cuff while intra arterial measurements of blood pressure are normal. Orthostatic hypertension is when blood pressure increases upon standing.

Once the diagnosis of hypertension has been made, healthcare providers should attempt to identify the underlying cause based on risk factors and other symptoms, if present. Secondary hypertension is more common in preadolescent children, with most cases caused by kidney disease. Primary or essential hypertension is more common in adolescents and has multiple risk factors, including obesity and a family history of hypertension. Laboratory tests can also be performed to identify possible causes of secondary hypertension, and to determine whether hypertension has caused damage to the heart, eyes, and kidneys. Additional tests for diabetes and high cholesterol levels are usually performed because these conditions are additional risk factors for the development of heart disease and may require treatment.

Serum creatinine is measured to assess for the presence of kidney disease, which can be either the cause or the result of hypertension. Serum creatinine alone may overestimate glomerular filtration rate and recent guidelines advocate the use of predictive equations such as the Modification of Diet in Renal Disease (MDRD) formula to estimate glomerular filtration rate (eGFR). eGFR can also provide a baseline measurement of kidney function that can be used to monitor for side effects of certain anti-hypertensive drugs on kidney function. Additionally, testing of urine samples for protein is used as a secondary indicator of kidney disease. Electrocardiogram (EKG/ECG) testing is done to check for evidence that the heart is under strain from high blood pressure. It may also show whether there is thickening of the heart muscle (left ventricular hypertrophy) or whether the heart has experienced a prior minor disturbance such as a silent heart attack. A chest X-ray or an echocardiogram may also be performed to look for signs of heart enlargement or damage to the heart.

Diagnosis includes determining the clinical signs and the medical history, with inquiry into possible routes of exposure. Clinical toxicologists, medical specialists in the area of poisoning, may be involved in diagnosis and treatment.

The main tool in diagnosing and assessing the severity of lead poisoning is laboratory analysis of the blood lead level (BLL).

Blood film examination may reveal basophilic stippling of red blood cells (dots in red blood cells visible through a microscope), as well as the changes normally associated with iron-deficiency anemia (microcytosis and hypochromasia). However, basophilic stippling is also seen in unrelated conditions, such as megaloblastic anemia caused by vitamin B12 (colbalamin) and folate deficiencies.

Exposure to lead also can be evaluated by measuring erythrocyte protoporphyrin (EP) in blood samples. EP is a part of red blood cells known to increase when the amount of lead in the blood is high, with a delay of a few weeks. Thus EP levels in conjunction with blood lead levels can suggest the time period of exposure; if blood lead levels are high but EP is still normal, this finding suggests exposure was recent. However, the EP level alone is not sensitive enough to identify elevated blood lead levels below about 35 μg/dL. Due to this higher threshold for detection and the fact that EP levels also increase in iron deficiency, use of this method for detecting lead exposure has decreased.

Blood lead levels are an indicator mainly of recent or current lead exposure, not of total body burden. Lead in bones can be measured noninvasively by X-ray fluorescence; this may be the best measure of cumulative exposure and total body burden. However this method is not widely available and is mainly used for research rather than routine diagnosis. Another radiographic sign of elevated lead levels is the presence of radiodense lines called lead lines at the metaphysis in the long bones of growing children, especially around the knees. These lead lines, caused by increased calcification due to disrupted metabolism in the growing bones, become wider as the duration of lead exposure increases. X-rays may also reveal lead-containing foreign materials such as paint chips in the gastrointestinal tract.

Fecal lead content that is measured over the course of a few days may also be an accurate way to estimate the overall amount of childhood lead intake. This form of measurement may serve as a useful way to see the extent of oral lead exposure from all the diet and environmental sources of lead.

Lead poisoning shares symptoms with other conditions and may be easily missed. Conditions that present similarly and must be ruled out in diagnosing lead poisoning include carpal tunnel syndrome, Guillain–Barré syndrome, renal colic, appendicitis, encephalitis in adults, and viral gastroenteritis in children. Other differential diagnoses in children include constipation, abdominal colic, iron deficiency, subdural hematoma, neoplasms of the central nervous system, emotional and behavior disorders, and intellectual disability.

Recently published evidence suggest heat stress and strenuous activity-induced cyclic uricosuria and crystalluria as a possible mechanism for the tubular lesion.