The signs and symptoms of primary hyperparathyroidism are those of hypercalcemia. They are classically summarized by "stones, bones, abdominal groans, thrones and psychiatric overtones".

- "Stones" refers to kidney stones, nephrocalcinosis, and diabetes insipidus (polyuria and polydipsia). These can ultimately lead to renal failure.

- "Bones" refers to bone-related complications. The classic bone disease in hyperparathyroidism is osteitis fibrosa cystica, which results in pain and sometimes pathological fractures. Other bone diseases associated with hyperparathyroidism are osteoporosis, osteomalacia, and arthritis.

- "Abdominal groans" refers to gastrointestinal symptoms of constipation, indigestion, nausea and vomiting. Hypercalcemia can lead to peptic ulcers and acute pancreatitis. The peptic ulcers can be an effect of increased gastric acid secretion by hypercalcemia.

- "Thrones" refers to polyuria and constipation

- "Psychiatric overtones" refers to effects on the central nervous system. Symptoms include lethargy, fatigue, depression, memory loss, psychosis, ataxia, delirium, and coma.

Left ventricular hypertrophy may also be seen.

Other signs include proximal muscle weakness, itching, and band keratopathy of the eyes.

When subjected to formal research, symptoms of depression, pain, and gastric dysfunction seem to correlate with mild cases of hypercalcemia.

Symptoms depend on whether the hyperparathyroidism is the result of parathyroid overactivity or secondary.

In primary hyperparathyroidism about 75% of people have no symptoms. The problem is often picked up during blood work for other reasons via a raised calcium. Many other people only have non-specific symptoms. Symptoms directly due to hypercalcemia are relatively rare, being more common in patients with malignant hypercalcemia. If present, common manifestations of hypercalcemia include weakness and fatigue, depression, bone pain, muscle soreness (myalgias), decreased appetite, feelings of nausea and vomiting, constipation, polyuria, polydipsia, cognitive impairment, kidney stones (See Foot Note) and osteoporosis. A history of acquired racquet nails (brachyonychia) may be indicative of bone resorption. Parathyroid adenomas are very rarely detectable on clinical examination. Surgical removal of a parathyroid tumor eliminates the symptoms in most patients.

In secondary hyperparathyroidism the parathyroid gland is behaving normally; clinical problems are due to bone resorption and manifest as bone syndromes such as rickets, osteomalacia and renal osteodystrophy.

In contrast with primary hyperparathyroidism in adults, primary hyperparathyroidism in pediatric patients is considered a rare endocrinopathy. Pediatric primary hyperparathyroidism can be distinguished by its more severe manifestations, in contrast to the less intense manifestations in adult primary hyperparathyroidism. Multiple endocrine neoplasia is more likely to be associated with childhood and adolescent primary hyperparathyroidism. The fundamental skeletal radiologic manifestation include diffuse osteopenia, pathologic fractures and the coexistence of resorption and sclerosis at numerous sites. Skeletal lesions can be specifically bilateral, symmetric and multifocal, exhibiting different types of bone resorption. Pathologic fractures of the femoral neck and spine can potentially initiate serious complications. Because pediatric primary hyperparathyroidism is frequently associated with pathologic fractures it can be misdiagnosed as osteogenesis imperfecta. Pediatric patients with primary hyperparathyroidism are best remedied by parathyroidectomy. Early diagnosis of pediatric primary hyperparathyroidism is all-important to minimize disease complications and start off timely and relevant treatment.

Hyperparathyroidism is an increased parathyroid hormone (PTH) levels in the blood. This occurs either from the parathyroid glands inappropriately making too much PTH (primary hyperparathyroidism) or other events triggering increased production by the parathyroid glands (secondary hyperparathyroidism). Most people with primary disease have no symptoms at the time of diagnosis. In those with symptoms the most common is kidney stones with other potential symptoms including weakness, depression, bone pains, confusion, and increased urination. Both types increase the risk of weak bones.

Primary hyperparathyroidism in 80% of cases is due to a single benign tumor known as a parathyroid adenoma with most of the rest of the cases due to a multiple benign tumors. Rarely it may be due to parathyroid cancer. Secondary hyperparathyroidism typically occurs due to vitamin D deficiency, chronic kidney disease, or other causes of low blood calcium. Diagnosis of primary disease is by finding a high blood calcium and high PTH levels.

Primary hyperparathyroidism may be cured by removing the adenoma or overactive parathyroid glands. In those without symptoms, mildly increased blood calcium levels, normal kidneys, and normal bone density monitoring may be all that is required. The medication cinacalcet may also be used to decrease PTH levels. In those with very high blood calcium levels treatment may include large amounts of intravenous normal saline. Low vitamin D levels should be corrected.

Primary hyperparathyroidism is the most common form. In the developed world between one and four per thousand people are affected. It occurs three times more often in women than men and is typically diagnosed between the ages of 50 and 60. The disease was first described in the 1700s and in the late 1800s was determined to be related to the parathyroid. Surgery as a treatment was first carried out in 1925.

The major symptoms of OFC are bone pain or tenderness, bone fractures, and skeletal deformities such as bowing of the bones. The underlying hyperparathyroidism may cause kidney stones, nausea, constipation, fatigue and weakness. X-rays may indicate thin bones, fractures, bowing, and cysts. Fractures are most commonly localized in the arms, legs, or spine.

The addition of weight loss, appetite loss, vomiting, polyuria, and polydipsia to the aforementioned symptoms may indicate that OFC is the result of parathyroid carcinoma. Parathyroid carcinoma, an uncommon cancer of the parathyroid glands, is generally indicated by serum calcium levels higher than usual, even in comparison to the high serum calcium levels that OFC generally presents with. Symptoms are also often more severe. Generally, the presence of a palpable neck mass is also indicative of the cancer, occurring in approximately 50% of sufferers, but virtually nonexistent in individuals with OFC with a different origin.

Bone and joint pain are common, as are limb deformities. The elevated PTH has also pleiotropic effects on the blood, immune system, and neurological system.

Secondary hyperparathyroidism (SHPT) refers to the excessive secretion of parathyroid hormone (PTH) by the parathyroid glands in response to hypocalcemia (low blood calcium levels) and associated hyperplasia of the glands. This disorder is especially seen in patients with chronic kidney failure. It is often—although not consistently—abbreviated as SHPT in medical literature.

Osteitis fibrosa cystica is defined as the classic skeletal manifestation of advanced hyperparathyroidism. Under the ICD-10 classification system, established by the World Health Organization, OFC is listed under category E21.0, primary hyperparathyroidism.

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.

Most cases of familial hypocalciuric hypercalcemia are asymptomatic. Laboratory signs of FHH include:

- Hypercalcemia

- Hypocalciuria ( Ca excretion rate < 0.02 mmol/L)

- Hypermagnesemia

- High normal to mildly elevated parathyroid hormone

Familial hypocalciuric hypercalcemia (FHH) is a condition that can cause hypercalcemia, a serum calcium level typically above 10.2 mg/dL. It is also known as familial benign hypocalciuric hypercalcemia (FBHH) where there is usually a family history of hypercalcemia which is mild, a urine calcium to creatinine ratio <0.01, and urine calcium <200 mg/day.

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.

Hypocalcemia is common and can occur unnoticed with no symptoms or, in severe cases, can have dramatic symptoms and be life-threatening. Hypocalcemia can be parathyroid related or vitamin D related. Parathyroid related hypocalcemia includes post-surgical hypoparathyroidism, inherited hypoparathyroidism, pseudohypoparathyroidism, and pseudo-pseudohypoparathyroidism. Post-surgical hypoparathyroidism is the most common form, and can be temporary (due to suppression of tissue after removal of a malfunctioning gland) or permanent, if all parathyroid tissue has been removed. Inherited hypoparathyroidism is rare and is due to a mutation in the calcium sensing receptor. Pseudohypoparathyroidism is maternally inherited and is categorized by hypocalcemia and hyperphosphatemia. Finally, pseudo-pseudohypoparathyroidism is paternally inherited. Patients display normal parathyroid hormone action in the kidney, but exhibit altered parathyroid hormone action in the bone.

Vitamin D related hypocalcemia may be associated with a lack of vitamin D in the diet, a lack of sufficient UV exposure, or disturbances in renal function. Low vitamin D in the body can lead to a lack of calcium absorption and secondary hyperparathyroidism (hypocalcemia and raised parathyroid hormone). Symptoms of hypocalcemia include numbness in fingers and toes, muscle cramps, irritability, impaired mental capacity and muscle twitching.

Many conditions are associated with disorders of the function of the parathyroid gland. Parathyroid diseases can be divided into those causing hyperparathyroidism, and those causing hypoparathyroidism.

Renal osteodystrophy may exhibit no symptoms; if it does show symptoms, they include:

- Bone pain

- Joint pain

- Bone deformation

- Bone fracture

- The broader concept of chronic kidney disease-mineral and bone disorder (CKD-MBD) is not only associated with fractures but also with cardiovascular calcification, poor quality of life and increased morbidity and mortality in CKD patients (the so-called bone-vascular axis). These clinical consequences are acquiring such an importance that scientific working groups (such as the ERA-EDTA CKD-MBD Working Group) or international initiatives are trying to promote research in the field including basic, translational and clinical research.

The first signs of a parathyroid adenoma and the resulting primary hyperparathyroidism can include bone fractures and urinary calculi such as kidney stones.

Oftentimes parathyroid adenoma is not diagnosed until found on standard blood-tests that reveal high calcium content in the blood, it can appear in urine tests as well. Patients may not be experiencing any noticeable symptoms but could be producing excessive amounts of calcium and eventually experience problems later in life if untreated. However, patients can experience common symptoms that can range from joint, muscle, and abdominal pain to slight discomfort. Additionally patients might be experiencing feelings of depression due to the hormonal imbalance. Constipation and exhaustion can also be experienced as a result of the irregularity in the bloodstream. There is also a potential that the kidneys could be damaged with the excess of calcium in the blood.

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.

A parathyroid adenoma is a benign tumor of the parathyroid gland. It generally causes hyperparathyroidism; there are very few reports of parathyroid adenomas that were not associated with hyperparathyroidism.

A human being usually has four parathyroid glands located on the back surface of the thyroid in the neck. The parathyroids secrete parathyroid hormone (PTH), which increases the concentration of calcium in the blood by inducing the bones to release calcium into the blood and the kidneys to reabsorb it from the urine into the blood. When a parathyroid adenoma causes hyperparathyroidism, more parathyroid hormone is secreted, causing the calcium concentration of the blood to rise, resulting in hypercalcemia.

Renal osteodystrophy is currently defined as an alteration of bone morphology in patients with chronic kidney disease (CKD). It is one measure of the skeletal component of the systemic disorder of chronic kidney disease-mineral and bone disorder (CKD-MBD). The term "renal osteodystrophy" was coined in 1943, 60 years after an association was identified between bone disease and renal failure. The traditional types of renal osteodystrophy have been defined on the basis of turnover and mineralization as follows: mild, slight increase in turnover and normal mineralization; osteitis fibrosa, increased turnover and normal mineralization; osteomalacia, decreased turnover and abnormal mineralization; adynamic, decreased turnover and acellularity; mixed, increased turnover with abnormal mineralization. A Kidney Disease: Improving Global Outcomes report has suggested that bone biopsies in patients with CKD should be characterized by determining bone turnover, mineralization, and volume (TMV system). On the other hand, CKD-MBD is defined as a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following: 1) abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism; 2) abnormalities in bone turnover, mineralization, volume, linear growth, or strength (renal osteodystrophy); and 3) vascular or other soft-tissue calcification.

Most patients experience moderate to severe hypercalcemia and high parathyroid hormone levels. A large mass in the neck is often seen, and renal and bone abnormalities are common.

The neuromuscular symptoms of hypercalcemia are caused by a negative bathmotropic effect due to the increased interaction of calcium with sodium channels. Since calcium blocks sodium channels and inhibits depolarization of nerve and muscle fibers, increased calcium raises the threshold for depolarization. This results in diminished deep tendon reflexes (hyporeflexia), and skeletal muscle weakness. There is a general mnemonic for remembering the effects of hypercalcaemia: "Stones, Bones, Groans, Thrones and Psychiatric Overtones"

- Stones (renal or biliary) (see calculus)

- Bones (bone pain)

- Groans (abdominal pain, nausea and vomiting)

- Thrones (polyuria) resulting in dehydration

- Psychiatric overtones (Depression 30–40%, anxiety, cognitive dysfunction, insomnia, coma)

Other symptoms include cardiac arrhythmias (especially in those taking digoxin), fatigue, nausea, vomiting (emesis), anorexia, abdominal pain, constipation, & paralytic ileus. If renal impairment occurs as a result, manifestations can include polyuria, nocturia, and polydipsia. Psychiatric manifestation can include emotional instability, confusion, delirium, psychosis, & stupor. Limbus sign seen in eye due to hypercalcemia.

Hypercalcemia can result in an increase in heart rate and a positive inotropic effect (increase in contractility).

Symptoms are more common at high calcium blood values (12.0 mg/dL or 3 mmol/l). Severe hypercalcaemia (above 15–16 mg/dL or 3.75–4 mmol/l) is considered a medical emergency: at these levels, coma and cardiac arrest can result. The high levels of calcium ions decrease the neuron membrane permeability to sodium ions, thus decreasing excitability, which leads to hypotonicity of smooth and striated muscle. This explains the fatigue, muscle weakness, low tone and sluggish reflexes in muscle groups. The sluggish nerves also explain drowsiness, confusion, hallucinations, stupor and / or coma. In the gut this causes constipation. Hypocalcaemia causes the opposite by the same mechanism.

Metastatic calcification is deposition of calcium salts in otherwise normal tissue, because of elevated serum levels of calcium, which can occur because of deranged metabolism as well as increased absorption or decreased excretion of calcium and related minerals, as seen in hyperparathyroidism.

In contrast, dystrophic calcification is caused by abnormalities or degeneration of tissues resulting in mineral deposition, though blood levels of calcium remain normal. These differences in pathology also mean that metastatic calcification is often found in many tissues throughout a person or animal, whereas dystrophic calcification is localized.

Metastatic calcification can occur widely throughout the body but principally affects the interstitial tissues of the vasculature, kidneys, lungs, and gastric mucosa. For the latter three, acid secretions or rapid changes in pH levels contribute to the formation of salts.

Primary hyperparathyroidism and malignancy account for about 90% of cases of hypercalcaemia.

Chronic kidney disease–mineral and bone disorder (CKD-MBD) is one of the many complications associated with chronic kidney disease. It represents a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following:

- Abnormalities of calcium, phosphorus (phosphate), parathyroid hormone, or vitamin D metabolism

- Abnormalities in bone turnover, mineralization, volume, linear growth, or strength

- Vascular or other soft-tissue calcification

CKD-MBD explains, at least in part, the high morbidity and mortality of CKD patients, linking kidney and bone disease with cardiovascular complications. It is a matter of discussion whether CKD-MBD may be considered a real syndrome or not.

CKD-MBD broadens the "old" concept of "renal osteodystrophy", which now should be restricted to describing the "bone pathology" associated with CKD. Thus, renal osteodystrophy is currently considered "one" measure of the skeletal component of the systemic disorder of CKD–MBD that is quantifiable by histomorphometry of bone biopsy.

Brown tumours consist of fibrous tissue, woven bone and supporting vasculature, but no matrix. The osteoclasts consume the trabecular bone that osteoblasts lay down and this front of reparative bone deposition followed by additional resorption can expand beyond the usual shape of the bone, involving the periosteum thus causing bone pain. The characteristic brown coloration results from hemosiderin deposition into the osteolytic cysts. Hemosiderin deposition is not a distinctive feature of brown tumors; it may also be seen in giant cell tumors of the bone.

Brown tumors may be rarely associated with ectopic parathyroid adenomas or end stage renal osteodystrophy.