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.

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.

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.

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.

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.

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.

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.

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.

People often have few or no symptoms. They may get occasional muscular weakness, muscle spasms, tingling sensations, or excessive urination.

High blood pressure, manifestations of muscle cramps (due to hyperexcitability of neurons secondary to low blood calcium), muscle weakness (due to hypoexcitability of skeletal muscles secondary to hypokalemia), and headaches (due to low blood potassium or high blood pressure) may be seen.

Secondary hyperaldosteronism is often related to decreased cardiac output which is associated with elevated renin levels.

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.

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.

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

Primary aldosteronism, also known as primary hyperaldosteronism or Conn's syndrome, is excess production of the hormone aldosterone by the adrenal glands resulting in low renin levels. Often it produces few symptoms. Most people have high blood pressure which may cause poor vision or headaches. Occasionally there may be muscular weakness, muscle spasms, tingling sensations, or excessive urination. Complications include cardiovascular disease such as stroke, myocardial infarction, kidney failure, and abnormal heart rhythms.

Primary hyperaldosteronism has a number of causes. About 66% of cases are due to enlargement of both adrenal glands and 33% of cases are due to an adrenal adenoma that produces aldosterone. Other uncommon causes include adrenal cancer and an inherited disorder called familial hyperaldosteronism. Some recommend screening people with high blood pressure who are at increased risk while others recommend screening all people with high blood pressure for the disease. Screening is usually done by measuring the aldosterone-to-renin ratio in the blood with further testing used to confirm positive results. While low blood potassium is classically described this is only present in about a quarter of people. To determine the underlying cause medical imaging is carried out.

Some cases may be cured by removing the adenoma by surgery. A single adrenal gland may also be removed in cases where only one is enlarged. In cases due to enlargement of both glands treatment is typically with medications known as aldosterone antagonists such as spironolactone or eplerenone. Other medications for high blood pressure and a low salt diet may also be needed. Some people with familial hyperaldosteronism may be treated with the steroid dexamethasone.

Primary aldosteronism is present in about 10% of people with high blood pressure. It occurs more often in women than men. Often it begins in those between 30 and 50 years of age. Conn's syndrome is named after Jerome W. Conn (1907–1994), the American endocrinologist who first described adenomas as a cause of the condition in 1955.

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.

Blood levels of parathryoid hormone (PTH) are undetectable, but the mutation in the PTHR1 leads to auto-activation of the signaling as though the hormone PTH is present. Severe JMC produces a dwarfing phenotype, or short stature. Examination of the bone reveals normal epiphyseal plates but disorganized metaphyseal regions. Hypercalcemia (elevated levels of calcium in the blood) and hypophosphatemia (reduced blood levels of phosphate), and elevated urinary calcium and phosphate are generally found in JMC. The absence of hypercalcemia does not eliminate the disease from consideration.

Physical irregularities often associated with Jansen's include: prominent or protruding eyes, a high-arched palate, micrognathia or abnormal smallness of the jaws – particularly the lower (mandible) jaw, choanal stenosis, wide cranial sutures and irregular formation of the long bones which can resemble rickets. Nephrocalcinosis (accumulation of calcium in the interstitum of the kidney) is seen commonly as well.

The lack of vasopressin production usually results from some sort of damage to the pituitary gland. It may be caused due to damage to the brain caused by:

- Benign suprasellar tumors (20% of cases)

- Infections (encephalitis, tuberculosis etc.)

- Trauma (17% of cases) or neurosurgery (9% of cases)

- Non-infectious granuloma (sarcoidosis, Langerhans cell histiocytosis etc.)

- Leukaemia

- Autoimmune - associated with thyroiditis

- Other rare causes which include hemochromatosis and histiocytosis.

Vasopressin is released by the posterior pituitary, but unlike most other pituitary hormones, vasopressin is produced in the hypothalamus. Neurogenic diabetes insipidus can be a failure of production at the hypothalamus, or a failure of release at the pituitary.

Central diabetes insipidus, also called neurogenic diabetes insipidus, is a type of diabetes insipidus due to a lack of vasopressin (ADH) production in the brain. Vasopressin acts to increase the volume of blood (intravascularly), and decrease the volume of urine produced. Therefore, a lack of it causes increased urine production and volume depletion.

It is also known as neurohypophyseal diabetes insipidus, referring to the posterior pituitary (neurohypophysis), which is supplied by the hypothalamus in the brain. This condition has only polyuria in common with diabetes and although not mutually exclusive, with most typical cases, the name diabetes insipidus is a misleading misnomer. A better name might be "hypothalamic-neurohypophyseal ADH deficiency".

Jansen's metaphyseal chondrodysplasia (JMC) is a disease that results from ligand-independent activation of the type 1 of the parathyroid hormone receptor (PTHR1), due to one of three reported mutations (activating mutation).

JMC is extremely rare, and as of 2007 there are fewer than 20 reported cases worldwide.

Adrenal crisis is caused by a deficiency of cortisol resulting from Addison's disease, congenital adrenal hyperplasia (CAH), corticosteroid biosynthetic enzyme defects or pituitary disorders (such as Sheehan's syndrome, pituitary adenoma, hypopituitarism (inactive or underactive pituitary) causing failure to activate the adrenal glands.

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.

Characteristic symptoms are:

- Sudden penetrating pain in the legs, lower back or abdomen

- Confusion, psychosis, slurred speech

- Severe lethargy

- Convulsions

- Fever

- Hyperkalemia (elevated potassium level in the blood)

- Hypercalcemia (elevated calcium level in the blood): the cause of hypercalcemia is a combination of increased calcium input into the extracellular space and reduced calcium removal by the kidney, this last caused by decreased glomerular filtration and increased tubular calcium reabsorption. Both renal factors are secondary to volume depletion and, in fact, improve rapidly during rehydration with saline infusion.

- Hypoglycemia (reduced level of blood glucose)

- Hyponatremia (low sodium level in the blood)

- Hypotension (low blood pressure)

- Hypothyroid (low T4 level)

- Severe vomiting and diarrhea, resulting in dehydration

- Syncope (loss of consciousness and ability to stand)

Hyperparathyroidism is present in ≥ 90% of patients. Asymptomatic hypercalcemia is the most common manifestation: about 25% of patients have evidence of nephrolithiasis or nephrocalcinosis. In contrast to sporadic cases of hyperparathyroidism, diffuse hyperplasia or multiple adenomas are more common than solitary adenomas.