Primary parathyroid hyperplasia
Synonyms and keywords: Hyperplasia of the parathyroid gland; Nodular hyperplasia; Multiple adenomatosis; Chief cell hyperplasia; Parathyroid gland hyperplasia

# Overview
Parathyroid hyperplasia is the diffuse enlargement of the parathyroid glands. Parathyroid hyperplasia causes hyperparathyroidism. Parathyroid hyperplasia may be classified into 2 subtypes: primary parathyroid hyperplasia and secondary parathyroid hyperplasia. Parathyroid hyperplasia must be differentiated from parathyroid adenoma and parathyroid carcinoma. Females are more commonly affected with parathyroid hyperplasia than males. Symptoms of parathyroid hyperplasia include constipation, nausea, and muscle pain. An elevated concentration of serum calcium,  magnesium, and parathormone and decreased phosphorous are diagnostics of parathyroid hyperplasia. Surgery is the mainstay of treatment for parathyroid hyperplasia.

# Classification
- Parathyroid hyperplasia may be classified into 2 subtypes:
- Primary parathyroid hyperplasia
- Secondary parathyroid hyperplasia

# Pathophysiology
- Parathyroid hyperplasia is the diffuse enlargement of the parathyroid glands and is a cause of primary hyperparathyroidism.
- In ~50% of cases there is asymmetric enlargement of the parathyroid glands.

## Associated Conditions
- Parathyroid hyperplasia may be associated with:
- Multiple endocrine neoplasia type 1 (MEN I)
- Multiple endocrine neoplasia type 2 (MEN IIA)
- Isolated familial hyperparathyroidism

## Gross Pathology
- Classically all parathyroid glands are involved; however, some may be spared making it difficult to differentiate parathyroid hyperplasia from parathyroid adenoma.

## Microscopic Pathology
- On microscopic histopathological analysis characteristic findings of primary parathyroid hyperplasia include:
- An abundant adipose tissue composition
- The presence of water-clear cells ("water-clear cell hyperplasia")

# Causes
- Primary parathyroid hyperplasia
- Sporadic (80%): associated with exposure to radiation and lithium
- Familial (20%): associated with MEN 1 and MEN 2a
- The most common cause of secondary parathyroid hyperplasia is renal failure

# Differentiating Parathyroid hyperplasia from other Diseases
- Parathyroid hyperplasia must be differentiated from other diseases such as:
- Parathyroid adenoma
- Parathyroid carcinoma

# Epidemiology and Demographics

## Age
Females are more commonly affected with parathyroid hyperplasia than males. The female to male ratio is approximately 3:1.

# Risk Factors
- The following risk factors are associated with parathyroid hyperplasia:
- Multiple endocrine neoplasia type 1 (MEN I)
- Multiple endocrine neoplasia type 2 (MEN IIA)
- Isolated familial hyperparathyroidism

# Natural History, Complications and Prognosis
- Depending on the extent of the disease at the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as excellent.

## Complications
- Parathyroid hyperplasia is associated with the following complications:
- Kidney stones
- Osteitis fibrosa cystica

# Diagnosis

## History
- The frequency and amount of alcohol consumption should be characterized.

## Symptoms
- Parathyroid hyperplasia is associated with the following symptoms:
- Constipation
- Bone fractures or bone pain
- Nausea
- Lethargy
- Muscle pain

## Laboratory Findings
- Laboratory findings consistent with the diagnosis of parathyroid hyperplasia include:
- Elevated calcium
- Decreased phosphorus
- Elevated magnesium
- Elevated parathyroid hormone
- Elevated vitamin D levels
- Elevated 24-hour urine calcium levels

## Chest X-Ray
- Bone x-ray may be helpful in the diagnosis of parathyroid hyperplasia.

## Other Imaging Findings
- Bone density test (DXA) may be helpful in the diagnosis of parathyroid hyperplasia.
- Nuclear medicine (Tc-99m MIBI) is the current modality of choice.

# Treatment

## Surgery
- Surgery is the mainstay of treatment for parathyroid hyperplasia. Three and a half part of the glands are removed during surgery.

### Parathyroidectomy
- Patients with primary hyperparathyroidism and concordant localization to a single site can undergo minimally invasive parathyroidectomy. Patients with primary hyperparathyroidism where localization has not been successful are more likely to have multiple gland diseases and should undergo open parathyroidectomy and four-gland exploration. Patients with secondary and tertiary hyperparathyroidism require either subtotal parathyroidectomy or total parathyroidectomy with or without forearm autotransplantation. Successful detection and removal of the involved parathyroid tissue will occur in 98% of patients. In the small percentage of patients in whom the gland is not detected at the time of primary surgery, it is likely to lie in an ectopic position, e.g. pericardium or middle mediastinum and additional, localisation studies such as CT scanning and selective venous sampling will be required prior to a second operation.
- The complications of parathyroidectomy include all the general complications of any operation, such as bleeding, wound infection, and reaction to the anaesthetic agent. In addition, there are specific complications, including damage to the recurrent laryngeal nerves and to the external branch of the superior laryngeal nerves failure to locate abnormal parathyroid tissue hypoparathyroidism
- Recurrent nerve palsy leads to a hoarse voice that usually recovers but may require procedures such as vocal cord medialization. If the external branch of the superior laryngeal nerve is damaged, the patient may lose the ability to sing, shout, or project their voice. Failure to locate abnormal parathyroid tissue may be due to the adenoma being in an ectopic site such as the mediastinum. Further localization studies and surgery will be required. If more than one parathyroid gland is involved, subtotal parathyroidectomy may lead to hypoparathyroidism, which may require short-term administration of oral calcium and 1,25-dihydroxyvitamin D for several weeks.

## Secondary Prevention
- Genetic screening for patients with family history of MEN syndrome.