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.

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.

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

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.

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.

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

Treatment is usually surgical removal of the gland(s) containing adenomas, but medication may also be required.

Hyperparathyroidism is confirmed by blood tests such as calcium and PTH levels. A specific test for parathyroid adenoma is sestamibi parathyroid scintigraphy, the sestamibi scan. This nuclear imaging technique reveals the presence and location of pathological parathyroid tissue.

The single major disease of parathyroid glands is overactivity of one or more of the parathyroid lobes, which make too much parathyroid hormone, causing a potentially serious calcium imbalance. This is called hyperparathyroidism; it leads to hypercalcemia, kidney stones, osteoporosis, and various other symptoms. Hyperparathyroidism was first described in 1925 and the symptoms have collectively become known as "moans, groans, stones, and bones." By far, the most common symptom is fatigue, but depression, memory loss, and bone aches are also very common. Primary hyperparathyroidism is relatively more common in postmenopausal women. The primary treatment for this disease is the surgical removal of the faulty gland.

If a patient has elevated calcium, several different types of tests can be used to locate the abnormal glands. The most common and most accurate test to find a parathyroid tumor is the Sestamibi scan. The Sestamibi scan does not have high resolution. Neck ultrasound has higher resolution, but requires some expertise to perform. Ultrasound's shortcomings include: it cannot determine glandular function (normal vs. hyperfunctioning) or visualize unusual locations such as retropharyngeal or mediastinal. Thin cut computed tomography of the neck can reveal glands in locations that the ultrasound cannot evaluate well; e.g. retropharyngeal, mediastinal. These tests are ordered by an endocrinologist or a surgeon that specializes in parathyroid surgery. Often, these "localizing" tests used to "find" the bad parathyroid gland are not successful in locating which parathyroid gland has become a tumor. This often causes confusion for the patient and doctor, since the tumor was not located. This simply means that the tumor was not found using these tests; it does not mean the tumor does not exist. The use of ultrasound-guided FNA, and parathyroid hormone washings can confirm the abnormal glands. For decades, it has been known that the best way to find a parathyroid tumor is through a very experienced parathyroid surgeon.

Even if a patient has a non-localizing Sestamibi scan (a negative sestamibi scan), he/she should almost always have a neck exploration to remove the tumor if he/she has high calcium levels, among other symptoms. Minimally-invasive parathyroid surgery is becoming more available, but, depending on the expertise of the surgeon, the patient may need to have a positive sestamibi scan before a minimally-invasive operation is attempted. Some of the most experienced surgeons perform mini-parathyroid surgery on all patients, but this is available only at highly specialized centers. Some patients will need both sides of their necks explored to find the dysfunctional gland(s).

Another related condition is called secondary hyperparathyroidism (HPT for short), which is common in patients with chronic kidney disease on dialysis. In secondary HPT, the parathyroid glands make too much parathyroid hormone (PTH) because the kidneys have failed, and the calcium and phosphorus are out of balance. Even though one may not have any symptoms, treating secondary HPT is important. Cinacalcet (Sensipar) is a medicine that can help treat such dialysis patients and is available by prescription only. Most experts believe that Sensipar should not be used for patients with primary hyperparathyroidism (patients that have a high calcium and are not on kidney dialysis).

Parathyroid surgery is usually performed when there is hyperparathyroidism. This condition causes many diseases related with calcium reabsorption, because the principal function of the parathyroid hormone is to regulate it. Parathyroid surgery could be performed in two different ways: first is a complete parathyroidectomy, and second is the auto transplantation of the removed parathyroid glands. There are various conditions that can indicate the need for the removal or transplant of the parathyroid glands. Hyperparathyroidism is a condition caused by overproduction of PTH, and can be divided into three types.

- Primary hyperparathyroidism happens when the normal mechanism of regulation by negative feedback of calcium is interrupted, or in other words the amount of blood calcium would ordinarily signal less production of PTH. Most of the time this is caused by adenomas, hyperplasia or carcinomas.

- Secondary hyperparathyroidism normally occurs in patients that suffer renal disease. Poor kidney function leads to a mineral disequilibrium that causes the glands hypertrophy in order to synthesize and release more PTH.

- Tertiary hyperparathyroidism develops when the hyperplastic gland of secondary hyperparathyroidism constantly releases PTH, independent of the regulation systems.

Another condition is hypercalcemia, which refers to a calcium level above 10.5 mg/dL. Consequences of this are heart rhythm diseases, and extra production of gastrin that causes peptic ulcers.

Parathyroid transplant is recommended if the parathyroid glands are removed accidentally during a thyroidectomy. They are autotransplanted to the nearby sternocleidomastoid muscle, or to the forearm so that another intervention would be less risky. A biopsy is recommended to be sure that the transplanted tissue is parathyroid and not a lymph node with metastatic disease. During parathyroid surgery if there is an adenoma the transplantation is not recommended; instead it is cryopreserved for research an if there is a recurrent hypoparathyroidism.

The surgery is indicated for all patients that are diagnosed with hyperparathyroidism with or without symptoms, especially in younger patients. In some cases the surgery works as therapy for nephrolithiasis, bone changes, and neuromuscular symptoms.

Parathyroidectomy, or the removal of the parathyroids, requires general anesthesia. The patient is intubated and placed in a supine position with the chin at fifteen degrees by elevating the shoulders to permit the extension of the neck. Then a transverse cut is made above the sternal notch. The transversal thyroid lobe is reached and is rotated up to discover and ligate the thyroid vein to separate the thyroid artery. Exploration must be done meticulously to search for adenomas. If an adenoma is identified, exploration must be continued because it is common that more than one neoplasia appears. Before the procedure, the glands are marked to make them more visible during the procedure. If one of them cannot be found, the procedure is to remove a complete thyroid lobe on the side where the gland is not found to avoid an intrathyroid parathyroid gland. After exploration, if there is one, two or even three parathyroid glands affected, they are removed and the other one left in situ. If all four glands are affected then three and a half are removed. The remaining half is marked with a suture and the surgeon must be sure that the blood supply will not be compromised. A total parathyroidectomy or auto transplantation to the forearm of the remaining half gland, may also be recommended.

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.

Macroglossia is usually diagnosed clinically. Sleep endoscopy and imaging may be used for assessment of obstructive sleep apnea. The initial evaluation of all patients with macroglossia may involve abdominal ultrasound and molecular studies for Beckwith–Wiedemann syndrome.

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.

Almost all who undergo parathyroidectomy experience increased bone density and repair of the skeleton within weeks. Additionally, patients with OFC who have undergone parathyroidectomy begin to show regression of brown tumors within six months. Following parathyroidectomy, hypocalcaemia is common. This results from a combination of suppressed parathyroid glands due to prolonged hypercalcaemia, as well as the need for calcium and phosphate in the mineralization of new bone.

Thirty percent of patients with OFC caused by parathyroid carcinoma who undergo surgery see a local recurrence of symptoms. The post-surgical survival rate hovers around seven years, while patients who do not undergo surgery have a survival rate of around five years.

The diagnosis of harlequin-type ichthyosis relies on both physical examination and certain laboratory tests.

Physical assessment at birth is vital for the initial diagnosis of harlequin ichthyosis. Physical examination reveals characteristic symptoms of the condition especially the abnormalities in the skin surface of newborns. Abnormal findings in physical assessments usually result in employing other diagnostic tests to ascertain the diagnosis.

Genetic testing is the most specific diagnostic test for harlequin ichthyosis. This test reveals a loss of function mutation on the ABCA12 gene. This gene is important in the regulation of protein synthesis for the development of the skin layer. Mutations in the gene may cause impaired transport of lipids in the skin layer and may also lead to shrunken versions of the proteins responsible for skin development. Less severe mutations result in a collodion membrane and congenital ichthyosiform erythroderma-like presentation. ABCA12 is an ATP binding cassette (ABC) transporter, and is a member of a large family of proteins that hydrolyze ATP to transport cargo across membranes. ABCA12 is thought to be a lipid transporter in keratinocytes necessary for lipid transport into lamellar granules during the formation of the lipid barrier.

Biopsy of skin may be done to assess the histologic characteristics of the cells. Histological findings usually reveal hyperkeratotic skin cells, which leads to a thick, white and hard skin layer.

Surgery is the only cure for parathyroid adenomas. It is successful about 95% of the time. Parathyroidectomy is the removal of the affected gland(s). The standard of treatment of primary hyperparathyroidism was formerly a surgical technique called bilateral neck exploration, in which the neck was opened on both sides, the parathyroids were identified, and the affected tissue was removed. By the 1980s, unilateral exploration became more common. Parathyroidectomy can now be performed in a minimally invasive fashion, mainly because imaging techniques can pinpoint the location of the tissue. Minimally invasive techniques include smaller open procedures, radio-guided and video-assisted procedures, and totally endoscopic surgery.

Before surgery is attempted, the affected glandular tissue must be located. Though the parathyroid glands are usually located on the back of the thyroid, their position is variable. Some people have one or more parathyroid glands elsewhere in the neck anatomy or in the chest. About 10% of parathyroid adenomas are ectopic, located not along the back of the thyroid but elsewhere in the body, sometimes in the mediastinum of the chest. This can make them difficult to locate, so various imaging techniques are used, such as the sestamibi scan, single-photon emission computed tomography (SPECT), ultrasound, MRI, and CT scans. sometimes parathyroid adenomas can be ablated by ethanol injection, guided by ultrasound.

Parathyroid carcinoma is sometimes diagnosed during surgery for primary hyperparathyroidism. If the surgeon suspects carcinoma based on severity or invasion of surrounding tissues by a firm parathyroid tumor, aggressive excision is performed, including the thyroid and surrounding tissues as necessary.

Agents such as calcimimetics (for example, cinacalcet) are used to mimic calcium and are able to activate the parathyroid calcium-sensing receptor (making the parathyroid gland "think" we have more calcium than we actually do), therefore lowering the calcium level, in an attempt to decrease the hypercalcemia.

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.

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.

Hypophosphatemia is diagnosed by measuring the concentration of phosphate in the blood. Concentrations of phosphate less than 0.81 mmol/L (2.5 mg/dL) are considered diagnostic of hypophosphatemia, though additional tests may be needed to identify the underlying cause of the disorder.

There is no diagnostic test for calciphylaxis. The diagnosis is a clinical one. The characteristic lesions are the ischemic skin lesions (usually with areas of skin necrosis). The necrotic skin lesions (i.e. the dying or already dead skin areas) typically appear as violaceous (dark bluish purple) lesions and/or completely black leathery lesions. They can be extensive. The suspected diagnosis can be supported by a skin biopsy. It shows arterial calcification and occlusion in the absence of vasculitis. Sometimes the bone scintigraphy can show increased tracer accumulation in the soft tissues. In certain patients, anti-nuclear antibody may play a role.

Recovery from renal osteodystrophy has been observed following kidney transplantation. Renal osteodystrophy is a chronic condition with a conventional hemodialysis schedule. Nevertheless, it is important to consider that the broader concept of CKD-MBD, which includes renal osteodystrophy, is not only associated with bone disease and increased risk of fractures but also with cardiovascular calcification, poor quality of life and increased morbidity and mortality in CKD patients (the so-called bone-vascular axis). Actually, bone may now be considered a new endocrine organ at the heart of CKD-MBD.

Congenital lactic acidosis can be suspected based on blood or cerebrospinal fluid tests showing high levels of lactate; the underlying genetic mutation can only be diagnosed with genetic testing.

The diagnosis of hyperphosphatemia is made through measuring the concentration of phosphate in the blood. A phosphate concentration greater than 1.46 mmol/L (4.5 mg/dL) is indicative of hyperphosphatemia, though further tests may be needed to identify the underlying cause of the elevated phosphate levels.

Tertiary hyperparathyroidism is a state of excessive secretion of parathyroid hormone (PTH) after a long period of secondary hyperparathyroidism and resulting in a high blood calcium level. It reflects development of autonomous (unregulated) parathyroid function following a period of persistent parathyroid stimulation.

The basis of treatment is still prevention in chronic kidney failure, starting medication and dietary restrictions long before dialysis treatment is initiated. Cinacalcet has greatly reduced the number of patients who ultimately require surgery for secondary hyperparathyroidism; however, approximately 5% of patients do not respond to medical therapy.

When secondary hyperparathyroidism is corrected and the parathyroid glands remain hyperfunctioning, it becomes tertiary hyperparathyroidism. The treatment of choice is surgical removal of three and one half parathyroid glands.