No treatment is generally required, as bone demineralisation and kidney stones are relatively uncommon in the condition.

As most cases of FHH are asymptomatic and benign, the diagnosis of FHH is less likely to be made.

Typically, diagnosis is made in the pursuit of uncovering the etiology of hypercalcemia.

Calcium levels are often in the high normal range or slightly elevated.

Commonly, the parathyroid hormone level is checked and may be slightly elevated or also on the high normal end.

Normally, high calcium should cause low PTH and so this level of PTH is inappropriately high due to the decreased sensitivity of the parathyroid to calcium.

This may be mistaken for primary hyperparathyroidism.

However, evaluation of urine calcium level will reveal a low level of urine calcium.

This too is inappropriate as high serum calcium should result in high urine calcium.

If urine calcium is not checked, this may lead to parathyroidectomy for presumed primary hyperparathyroidism.

Additionally as the name implies, there may be a family history of benign hypercalcemia.

Ultimately, diagnosis of familial hypocalciuric hypercalcemia is made — as the name implies — by the combination of low urine calcium and high serum calcium.

Abnormal heart rhythms can also result, and ECG findings of a short QT interval suggest hypercalcaemia. Significant hypercalcaemia can cause ECG changes mimicking an acute myocardial infarction. Hypercalcaemia has also been known to cause an ECG finding mimicking hypothermia, known as an Osborn wave.

Initial therapy:

- hydration, increasing salt intake, and forced diuresis.

- hydration is needed because many patients are dehydrated due to vomiting or kidney defects in concentrating urine.

- increased salt intake also can increase body fluid volume as well as increasing urine sodium excretion, which further increases urinary potassium excretion.

- after rehydration, a loop diuretic such as furosemide can be given to permit continued large volume intravenous salt and water replacement while minimizing the risk of blood volume overload and pulmonary oedema. In addition, loop diuretics tend to depress calcium reabsorption by the kidney thereby helping to lower blood calcium levels

- can usually decrease serum calcium by 1–3 mg/dL within 24 hours

- caution must be taken to prevent potassium or magnesium depletion

Because a significant portion of calcium is bound to albumin, any alteration in the level of albumin will affect the measured level of calcium. A corrected calcium level based on the albumin level is: Corrected calcium (mg/dL) = measured total Ca (mg/dL) + 0.8 * (4.0 - serum albumin [g/dL]).

The gold standard of diagnosis is the parathyroid immunoassay. Once an elevated Parathyroid hormone has been confirmed, goal of diagnosis is to determine whether the hyperparathyroidism is primary or secondary in origin by obtaining a serum calcium level:

Tertiary hyperparathyroidism has a high PTH and a high serum calcium. It is differentiated from primary hyperparathyroidism by a history of chronic kidney failure and secondary hyperparathyroidism.

Familial benign hypocalciuric hypercalcaemia can present with similarly lab changes. In this condition the calcium creatinine clearance ratio; however, is typically under 0.01.

The amount of biologically active calcium varies with the level of serum albumin, a protein to which calcium is bound, and therefore levels of "ionized calcium" are better measures than a "total calcium"; however, one can correct a "total calcium" if the albumin level is known.

- A normal "ionized calcium" is 1.12-1.45 mmol/L (4.54-5.61 mg/dL).

- A normal "total calcium" is 2.2-2.6 mmol/L (9-10.5 mg/dl).

- "Total calcium" of less than 8.0 mg/dL is hypocalcaemia, with levels below 1.59 mmol/L (6 mg/dL) generally fatal.

- "Total calcium" of more than 10.6 mg/dL is hypercalcaemia, with levels over 3.753 mmol/L (15.12 mg/dL) generally fatal.

Various investigations aid the diagnosis.

- ACTH (cosyntropin) stimulation test

- Cortisol level (to assess the level of glucocorticoids)

- Fasting blood sugar

- Serum potassium (to assess the level of mineralocorticoids)

- Serum sodium

Adrenal crisis is triggered by physiological stress (such as trauma). Activities that have an elevated risk of trauma are best avoided. Treatment must be given within two hours of trauma and consequently it is advisable to carry injectable hydrocortisone in remote areas.

Management of this condition includes|:

- Intravenous calcium gluconate 10% can be administered, or if the hypocalcaemia is severe, calcium chloride is given instead. This is only appropriate if the hypocalcemia is acute and has occurred over a relatively short time frame. But if the hypocalcemia has been severe and chronic, then this regimen can be fatal, because there is a degree of acclimatization that occurs. The neuromuscular excitability, cardiac electrical instability, and associated symptoms are then not cured or relieved by prompt administration of corrective doses of calcium, but rather exacerbated. Such rapid administration of calcium would result in effective over correction – symptoms of hypercalcemia would follow.

- However, in either circumstance, maintenance doses of both calcium and vitamin-D (often as 1,25-(OH)-D, i.e. calcitriol) are often necessary to prevent further decline

If the underlying cause of the hypocalcemia can be addressed, the hyperparathyroidism will resolve. In people with chronic renal failure, treatment consists of dietary restriction of phosphorus, supplements with an active form of vitamin D such as calcitriol, doxercalciferol, paricalcitol, etc. and phosphate binders which can be divided into calcium-based and non-calcium based.

Extended Release Calcifediol was recently approved by the FDA as a treatment for secondary hyperparathyroidism (SHPT) in adults with stage 3 or 4 chronic �kidney disease (CKD) and low vitamin D blood levels (25-hydroxyvitamin D less than 30 ng/mL). It can help treat SHPT by increasing Vitamin D levels and lowering parathyroid hormone or PTH. It is �not for patients with stage 5 CKD or on dialysis.

In the treatment of secondary hyperparathyroidism due to chronic kidney disease on dialysis calcimimetics do not appear to affect the risk of early death. It does decrease the need for a parathyroidectomy but caused more issues with low blood calcium levels and vomiting.

Most people with hyperparathyroidism secondary to chronic kidney disease will improve after renal transplantation, but many will continue to have a degree of residual hyperparathyroidism (tertiary hyperparathyroidism) post-transplant with associated risk of bone loss, etc.

The diagnosis of primary hyperparathyroidism is made by blood tests.

Serum calcium levels are elevated, and the parathyroid hormone level is abnormally high compared with an expected low level in response to the high calcium. A relatively elevated parathyroid hormone has been estimated to have a sensitivity of 60%-80% and a specificity of approximately 90% for primary hyperparathyroidism.

A more powerful variant of comparing the balance between calcium and parathyroid hormone is to perform a 3-hour calcium infusion. After infusion, a parathyroid hormone level above a cutoff of 14 ng/l has a sensitivity of 100% and a specificity of 93% in detecting primary hyperparathyroidism, with a confidence interval of 80% to 100%.

Urinary cAMP is occasionally measured; this is generally elevated.

Biochemical confirmation of primary hyperparathyroidism is following by investigations to localize the culprit lesion. Primary hyperparathyroidism is most commonly due to solitary parathyroid adenoma. Less commonly it may be due to double parathyroid adenomas or parathyroid hyperplasia. Tc99 sestamibi scan of head, neck and upper thorax is the most commonly used test for localizing parathyroid adenomas having a sensitivity and specificity of 70-80%. Sensitivity falls down to 30% in case of double/multiple parathyroid adenomas or in case of parathyroid hyperplasia. Ultrasonography is also a useful test in localizing suspicious parathyroid lesions.

Treatment involves having the person stop taking any calcium supplements and any other alkali agents they have been taking, and hydration.

In severe cases, hospitalization may be required, in which case saline may be administered intravenously.

If kidney failure is advanced then treatment for that is required, namely chronic dialysis.

In mild cases, full recovery is expected. In severe cases, permanent kidney failure or death may result.

If left untreated, the disease will progress to tertiary hyperparathyroidism, where correction of the underlying cause will not stop excess PTH secretion, i.e. parathyroid gland hypertrophy becomes irreversible. In contrast with secondary hyperparathyroidism, tertiary hyperparathyroidism is associated with hypercalcemia rather than hypocalcemia.

The surgical removal of one or more of the parathyroid glands is known as a parathyroidectomy; this operation was first performed in 1925. The symptoms of the disease, listed above, are indications for surgery. Surgery reduces all cause mortality as well as resolving symptoms. However, cardiovascular mortality is not significantly reduced.

The 2002 NIH Workshop on Asymptomatic Primary Hyperparathyroidism developed criteria for surgical intervention . The criteria were revised at the Third International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism . These criteria were chosen on the basis of clinical experience and observational and clinical trial data as to which patients are more likely to have end-organ effects of primary hyperparathyroidism (nephrolithiasis, skeletal involvement), disease progression if surgery is deferred, and the most benefit from surgery. The panel emphasized the need for parathyroidectomy to be performed by surgeons who are highly experienced and skilled in the operation. The Third International Workshop guidelines concluded that surgery is indicated in asymptomatic patients who meet any one of the following conditions:

- Serum calcium concentration of 1.0 mg/dL (0.25 mmol/L) or more above the upper limit of normal

- Creatinine clearance that is reduced to <60 mL/min

- Bone density at the hip, lumbar spine, or distal radius that is more than 2.5 standard deviations below peak bone mass (T score <-2.5) and/or previous fragility fracture

- Age less than 50 years

Operative intervention can be delayed in patients over 50 years of age who are asymptomatic or minimally symptomatic and who have serum calcium concentrations <1.0 mg/dL (0.2 mmol/L) above the upper limit of normal, and in patients who are medically unfit for surgery

More recently, three randomized controlled trials have studied the role of surgery in patients with asymptomatic hyperparathyroidism. The largest study reported that surgery resulted in an increase in bone mass, but no improvement in quality of life after one to two years among patients in the following groups:

- Untreated, asymptomatic primary hyperparathyroidism

- Serum calcium between 2.60–2.85 mmol/liter (10.4–11.4 mg/dl)

- Age between 50 and 80 yr

- No medications interfering with Ca metabolism

- No hyperparathyroid bone disease

- No previous operation in the neck

- Creatinine level < 130 µmol/liter (<1.47 mg/dl)

Two other trials reported improvements in bone density and some improvement in quality of life with surgery.

Hypercalcemia is suspected to occur in approximately 1 in 500 adults in the general adult population. Like hypocalcemia, hypercalcemia can be non-severe and present with no symptoms, or it may be severe, with life-threatening symptoms. Hypercalcemia is most commonly caused by hyperparathyroidism and by malignancy, and less commonly by vitamin D intoxication, familial hypocalciuric hypercalcemia and by sarcoidosis. Hyperparathyroidism occurs most commonly in postmenopausal women. Hyperparathyroidism can be caused by a tumor, or adenoma, in the parathyroid gland or by increased levels of parathyroid hormone due to hypocalcemia. Approximately 10% of cancer sufferers experience hypercalcemia due to malignancy. Hypercalcemia occurs most commonly in breast cancer, lymphoma, prostate cancer, thyroid cancer, lung cancer, myeloma, and colon cancer. It may be caused by secretion of parathyroid hormone-related peptide by the tumor (which has the same action as parathyroid hormone), or may be a result of direct invasion of the bone, causing calcium release.

Symptoms of hypercalcemia include anorexia, nausea, vomiting, constipation, abdominal pain, lethargy, depression, confusion, polyuria, polydipsia and generalized aches and pains.

Nephrocalcinosis is diagnosed for the most part by imaging techniques. The imagings used are ultrasound (US), abdominal plain film and CT imaging. Of the 3 techniques CT and US are the more preferred. Nephrocalcinosis is considered present if at least two radiologists make the diagnosis on US and/or CT. In some cases a renal biopsy is done instead if imaging is not enough to confirm nephrocalcinosis. Once the diagnosis is confirmed additional testing is needed to find the underlying cause because the underlying condition may require treatment for reasons independent of nephrocalcinosis. These additional tests will measure serum, electrolytes, calcium, and phosphate, and the urine pH. If no underlying cause can be found then urine collection should be done for 24 hours and measurements of the excretion of calcium, phosphate, oxalate, citrate, and creatinine are looked at.

As with hyperthyroidism, TSH is suppressed. Both free and serum (or total) T3 and T4 are elevated. An elevation in thyroid hormone levels is suggestive of thyroid storm when accompanied by signs of severe hyperthyroidism but is not diagnostic as it may also correlate with uncomplicated hyperthyroidism. Moreover, serum T3 may be normal in critically ill patients due to decreased conversion of T4 to T3. Other potential abnormalities include the following:

- Hyperglycemia likely due to catecholamine-mediated effects on insulin release and metabolism as well as increased glycogenolysis, evolving into hypoglycemia when glycogen stores are depleted

- Elevated aspartate aminotransferase (AST), bilirubin and lactate dehydrogenase (LDH)

- Hypercalcemia and elevated alkaline phosphatase due to increased bone resorption

- Elevated white blood cell count

In suspected cases of Addison's disease, demonstration of low adrenal hormone levels even after appropriate stimulation (called the ACTH stimulation test or synacthen test) with synthetic pituitary ACTH hormone tetracosactide is needed for the diagnosis. Two tests are performed, the short and the long test. It should be noted that dexamethasone does not cross-react with the assay and can be administered concomitantly during testing.

The short test compares blood cortisol levels before and after 250 micrograms of tetracosactide (intramuscular or intravenous) is given. If, one hour later, plasma cortisol exceeds 170 nmol/l and has risen by at least 330 nmol/l to at least 690 nmol/l, adrenal failure is excluded. If the short test is abnormal, the long test is used to differentiate between primary adrenal insufficiency and secondary adrenocortical insufficiency.

The long test uses 1 mg tetracosactide (intramuscular). Blood is taken 1, 4, 8, and 24 hr later. Normal plasma cortisol level should reach 1000 nmol/l by 4 hr. In primary Addison's disease, the cortisol level is reduced at all stages, whereas in secondary corticoadrenal insufficiency, a delayed but normal response is seen.

Other tests may be performed to distinguish between various causes of hypoadrenalism, including renin and adrenocorticotropic hormone levels, as well as medical imaging - usually in the form of ultrasound, computed tomography or magnetic resonance imaging.

Adrenoleukodystrophy, and the milder form, adrenomyeloneuropathy, cause adrenal insufficiency combined with neurological symptoms. These diseases are estimated to be the cause of adrenal insufficiency in about 35% of male patients with idiopathic Addison’s disease, and should be considered in the differential diagnosis of any male with adrenal insufficiency. Diagnosis is made by a blood test to detect very long chain fatty acids.

The diagnosis of thyroid storm is based on the presence of symptoms consistent with severe hyperthyroidism, as outlined in the Signs and symptoms section above. Multiple approaches have been proposed to calculate the probability of thyroid storm based on clinical criteria, however, none have been universally adopted by clinicians. For instance, Burch and Wartofsky published the Burch-Wartofsky point scale (BWPS) in 1993, assigning a numerical value based on the presence of specific signs and symptoms organized within the following categories: temperature, cardiovascular dysfunction (including heart rate and presence of atrial fibrillation or congestive heart failure), central nervous system (CNS) dysfunction, gastrointestinal or liver dysfunction and presence of a precipitating event. A Burch-Wartofsky score below 25 is not suggestive of thyroid storm whereas 25 to 45 suggests impending thyroid storm and greater than 45 suggests current thyroid storm. Alternatively, the Japanese Thyroid Association (JTA) criteria, derived from a large cohort of patients with thyroid storm in Japan and published in 2012, provide a qualitative method to determine the probability of thyroid storm. The JTA criteria separate the diagnosis of thyroid storm into definite versus suspected based on the specific combination of signs and symptoms a patient exhibits and require elevated free triiodothyronine (T3) or free thyroxine (T4) for definite thyroid storm.

Increasing fluid intake to yield a urine output of greater than 2 liters a day can be advantageous for all patients with nephrocalcinosis. Patients with hypercalciuria can reduce calcium excretion by restricting animal protein, limiting sodium intake to less than 100 meq a day and being lax of potassium intake. If changing ones diet alone does not result in an suitable reduction of hypercalciuria, a thiazide diuretic can be administered in patients who do not have hypercalcemia. Citrate can increase the solubility of calcium in urine and limit the development of nephrocalcinosis. Citrate is not given to patients who have urine pH equal to or greater than 7.

OFC may be diagnosed using a variety of techniques. Muscles in patients afflicted with OFC can either appear unaffected or "bulked up." If muscular symptoms appear upon the onset of hyperparathyroidism, they are generally sluggish contraction and relaxation of the muscles. Deviation of the trachea (a condition in which the trachea shifts from its position at the midline of the neck), in conjunction with other known symptoms of OFC can point to a diagnosis of parathyroid carcinoma.

Blood tests on patients with OFC generally show high levels of calcium (normal levels are considered to range between 8.5 and 10.2 mg/dL, parathyroid hormone (levels generally above 250 pg/mL, as opposed to the "normal" upper-range value of 65 pg/mL), and alkaline phosphatase(normal range is 20 to 140 IU/L).

X-rays may also be used to diagnose the disease. Usually, these X-rays will show extremely thin bones, which are often bowed or fractured. However, such symptoms are also associated with other bone diseases, such as osteopenia or osteoporosis. Generally, the first bones to show symptoms via X-ray are the fingers. Furthermore, brown tumors, especially when manifested on facial bones, can be misdiagnosed as cancerous. Radiographs distinctly show bone resorption and X-rays of the skull may depict an image often described as "ground glass" or "salt and pepper". Dental X-rays may also be abnormal.

Cysts may be lined by osteoclasts and sometimes blood pigments, which lend to the notion of "brown tumors." Such cysts can be identified with nuclear imaging combined with specific tracers, such as sestamibi. Identification of muscular degeneration or lack of reflex can occur through clinical testing of deep tendon reflexes, or via photomotogram (an achilles tendon reflex test).

Fine needle aspiration (FNA) can be used to biopsy bone lesions, once found on an X-ray or other scan. Such tests can be vital in diagnosis and can also prevent unnecessary treatment and invasive surgery. Conversely, FNA biopsy of tumors of the parathyroid gland is not recommended for diagnosing parathyroid carcinoma and may in fact be harmful, as the needle can puncture the tumor, leading to dissemination and the possible spread of cancerous cells.

The brown tumors commonly associated with OFC display many of the same characteristics of osteoclasts. These cells are characteristically benign, feature a dense, granular cytoplasm, and a nucleus that tends to be ovular in shape, enclosing comparatively fine chromatin. Nucleoli also tend to be smaller than average.

Vomiting and diarrhea are often the first clinical signs of grape or raisin toxicity. They often develop within a few hours of ingestion. Pieces of grapes or raisins may be present in the vomitus or stool. Further symptoms include weakness, not eating, increased drinking, and abdominal pain. Acute renal failure develops within 48 hours of ingestion. A blood test may reveal increases in blood urea nitrogen (BUN), creatinine, phosphorus, and calcium.