Parathyroid adenoma

    Last updated date: 02-Mar-2023

    Originally Written in English

    Parathyroid adenoma

    Parathyroid adenoma


    A noncancerous (benign) tumor of the parathyroid glands is known as a parathyroid adenoma. The parathyroid glands are found in the neck, close or connected to the thyroid gland on the rear side. Patients with primary hyperparathyroidism often have high serum calcium levels as well as elevated serum parathyroid hormone levels.


    Parathyroid adenoma definition

    Parathyroid adenoma definition

    A parathyroid adenoma is one of several types of parathyroid illness, including parathyroid hyperplasia and parathyroid cancer. Patients with a history of radiation therapy and long-term calcium deprivation are predisposed to parathyroid illness later in life.

    Primary, secondary, and tertiary hyperparathyroidism are the three types of hyperparathyroidism. The majority of parathyroid hyperplasia is caused by secondary hyperparathyroidism caused by renal illness. Tertiary hyperparathyroidism is defined as the independent production of parathyroid hormone in the presence of chronic renal illness that results in hypercalcemia. 

    Primary hyperparathyroidism is caused by parathyroid adenoma in 80-85% of cases, followed by primary parathyroid hyperplasia (15%) and parathyroid cancer (5%). 

    Patients with primary hyperparathyroidism may appear with non-specific symptoms such as tiredness, discomfort, and weakness, as well as polydipsia, polyuria, and nephrolithiasis. Constipation, anorexia, nausea, and vomiting are examples of gastrointestinal symptoms. Hypercalcemia can cause cardiac arrhythmias, unconsciousness, and death. Nowadays, most people with hypercalcemia are detected by chance during a regular work-up for another cause. Serum calcium levels are elevated in laboratory screening examinations. Radiographic examinations are used to evaluate patients, followed by a surgical investigation.

    Normal parathyroid glands are too tiny to be visible on imaging (generally 5 3 1 mm), however, parathyroid illness causes gland hypertrophy, permitting detection. The major imaging modalities used for the visualization of sick glands are sonography and 99mTc-sestamibi scintigraphy.

    On 2 h delayed pictures, there is a prolonged and enthusiastic absorption of sestamibi within adenomas. By permitting detection of enlarged parathyroid in three dimensions, single-photon emission computed tomography (SPECT) improves the sensitivity of localizing larger parathyroid glands by scintigraphy over planar imaging. Scintigraphy is roughly 90% sensitive for detecting a parathyroid adenoma and may readily detect glands larger than 500 mg.

    Combined SPECT/CT may potentially improve lesion localization, however preliminary results do not support this. Ultrasound imaging shows parathyroid adenomas as homogeneously hypoechoic lesions when compared to the neighboring thyroid, and they are easily spotted when they are bigger than 1 cm.

    Cystic parathyroid adenomas are uncommon, and the cystic areas present within the gland as areas of diminished echogenicity. Doppler imaging often shows a distinct extrathyroidal feeding artery entering the parathyroid gland at one of the poles.


    Parathyroid glands Anatomy

    Parathyroid glands Anatomy

    The parathyroid glands are tiny oval-shaped structures located near the thyroid. Eighty-five percent of individuals have four glands, two superior and two inferior. Superior glands (derived from the fourth branchial pouch) are often found on the posterior-lateral surface of the middle to superior thyroid lobe. Because of their embryological descent with the thymus (both originating from the third branchial pouch), the inferior glands can be discovered at any point along their line of development. They are most typically found in the inferior portion of the thyroid gland.

    A healthy parathyroid gland is around the size of an apple seed and weighs about 0.5 g. Microadenomas are tumors that weigh less than 0.1 g, whereas a big adenoma weighs more than 2 g. An adenoma weighs about 1 g on average.



    A single parathyroid adenoma accounts for 80 to 85 percent of hyperparathyroidism, with multiple adenomas accounting for 4 to 5 percent and parathyroid hyperplasia accounting for 10 to 12 percent. Thyroid carcinomas are extremely rare causes of hyperparathyroidism, accounting for fewer than 1% of cases. Adenomas are more frequent in persons aged 50 to 70, but they can arise at any age. Women are afflicted three times as frequently than males.



    A parathyroid adenoma is one of several types of parathyroid illness, including parathyroid hyperplasia and parathyroid cancer.

    For the majority of individuals, the cause of a parathyroid adenoma is unknown. The cyclin D1/PRAD1 gene is the most commonly related genetic mutation with sporadic adenomas. PTH secretion is affected when this gene's normal function is disrupted. Approximately 20 to 40% of spontaneous adenomas contain cyclin D1 overexpression. In terms of environmental variables, some evidence suggests that a patient's history of radiation therapy predisposes them to parathyroid illness later in life. Long-term calcium deprivation can potentially cause parathyroid illness owing to prolonged PTH activation. 



    By functioning in the kidneys, gut, and bone, parathyroid hormone is essential for calcium and phosphorus metabolism. PTH is normally released in response to low blood calcium levels and helps to promote calcium absorption in the distal tubules while inhibiting phosphate resorption. It also raises body calcium levels by indirectly activating osteoclasts, resulting in bone resorption.

    Finally, PTH improves calcium absorption in the intestine via boosting vitamin D activation. Pathological PTH overproduction will result in calcium increases and phosphate depletion. Derangements in these two components are responsible for the majority of the symptoms associated with parathyroid illness.



    Parathyroid adenoma symptoms

    Many people with a parathyroid adenoma are asymptomatic, with hypercalcemia detected by chance during normal blood testing. Symptoms of hypercalcemia, such as bone pain, tiredness, polyuria, nephrolithiasis, constipation, and neuropsychiatric disturbance, are the most prevalent manifestations of symptomatic parathyroid illness. Calcium elevations that are too high might result in problems such as cardiac arrhythmias, unconsciousness, and death.

    A patient is unlikely to have visible symptoms of a parathyroid adenoma. The diseased gland is seldom palpable, and a visible neck lump suggests thyroid pathology or parathyroid malignancy.



    The most frequent early symptom of hyperparathyroidism is hypercalcemia on normal blood work conducted for other reasons. Most individuals have moderate hypercalcemia, which may be intermittent and is generally less than 1.0 mg/dL over normal upper limits. Unexplained hypercalcemia on a repeat set of test results necessitates additional research. PTH levels should be checked afterwards, and they may be increased or even within normal ranges, which is inappropriate given the patient's hypercalcemia. Urine calcium levels can be tested every 24 hours, however this is not required for diagnosis.

    Radiographic imaging is the next stage in the assessment process. Imaging is critical because it not only informs surgical planning but also distinguishes between a single adenoma and a multi-gland hyperplastic condition.

    Because normal parathyroid glands are too tiny to be observed on ultrasonography, the presence of this gland should raise the possibility of a pathogenic condition. On ultrasonography, an adenoma should show as a homogeneously hypoechoic extrathyroidal oval mass with a fat plane separating it from normal thyroid tissue. A feeding artery may also be seen entering the adenoma's superior or inferior pole. Because it is operator-dependent, ultrasound has a sensitivity of just 60 to 80 percent. It might be used as a supplement to nuclear imaging.

    Single-radioisotope scintigraphy with technetium-99m (99mTc) combined with single-photon emission computed tomography (SPECT) imaging is the gold standard for parathyroid localization. SPECT is a three-dimensional sestamibi scan that increases visibility of the parathyroid glands. The combination of these approaches provides a sensitivity of 91 to 98 percent for detecting parathyroid adenomas.

    Dual-radioisotope imaging, which uses both 99mTc pertechnetate and thallium-201 (201Tl), is another option. Thallium is taken up by both the thyroid and the parathyroid, whereas pertechnetate is solely taken up by the thyroid. The glands are then seen using subtraction imaging. The need for a subtraction software, extended imaging periods, and limited vistas are all disadvantages of this technology. 

    Four-dimensional computed tomography (CT) and magnetic resonance imaging (MRI) have also been employed in parathyroid imaging. However, they are only 75% sensitive and 40% to 85% sensitive, respectively. As a result, nuclear imaging is used for preoperative localisation. Four-dimensional CT and MRI may be more useful in locating ectopic glands following unsuccessful parathyroidectomy.

    Immunohistochemical investigations are not usually required to make a diagnosis of parathyroid adenoma. Antibodies to chromogranin and parathyroid hormone bind to normal, hyperplasic, and malignant parathyroid tissue. However, due to significant diffusion artifact, parathyroid hormone staining is difficult to execute and interpret precisely. Immunohistochemical staining may be beneficial in distinguishing atypical parathyroid adenoma from parathyroid cancer.

    Adherence to thyroid tissue, vascular and capsular invasion, extension into soft tissue structures, trabecular growth pattern, dense fibrotic bands, thick fibrous tumor capsule, tumor necrosis, tumor cell spindling, prominent macronucleoli, increased mitotic activity, and atypical mitotic figures are all features to look for when diagnosing parathyroid carcinoma. There are situations when a parathyroid tumor has some histologic signs of carcinoma but lacks the whole range of features required to make the diagnosis.

    Finally, individuals with MEN syndromes, most typically MEN 1, frequently have parathyroid proliferative disease. Parathyroid hyperplasia affects over 90% of MEN 1 patients. These conditions can also include parathyroid adenoma and carcinoma. Although the great majority of individuals with parathyroid proliferative disorder have random illness, the potential of a MEN syndrome should always be considered when examining these patients.



    Parathyroid adenoma management

    Traditionally, the surgery of choice for hyperparathyroidism was bilateral 4-gland exploration. However, because a single adenoma accounts for 85 percent of the illness, minimally invasive parathyroidectomy is quickly becoming the gold standard for parathyroid adenoma.

    Due to PTH's short half-life, the Miami criterion requires that the PTH level decline by at least 50% within 10 minutes post adenoma excision. If this value is not fulfilled, more investigation is required. Glands that are missing can be located in the retropharyngeal or retro-esophageal planes, the posterior mediastinum, the thymus, the mediastinum, inside the thyroid capsule or gland, or in the carotid sheath.

    Calcium levels will decline over the following 2 to 4 days after parathyroidectomy, although few individuals will have symptoms. However, if symptoms arise, calcium gluconate therapy may be necessary. If the hypocalcemic condition persists, oral calcium supplementation will be required.


    Resection of parathyroid adenoma 

    Resection of parathyroid adenoma 

    During parathyroid adenoma excision, the surgeon is usually able to clearly identify the single swollen gland. Previously, additional glands had to be sampled to rule out parathyroid hyperplasia. With the precision of radiographic imaging and intraoperative parathyroid hormone monitoring, the surgeon no longer needs to collect tissue from the remaining glands. On physical inspection, the gland is clearly enlarged and substantial. However, like in this example, parathyroid adenoma can be cystic in rare cases.

    The weight of parathyroid adenomas varies, however the average weight for a parathyroid adenoma is about 1 g. (the weight of a normal parathyroid gland is typically less than 50 mg). The cut surface is usually smooth, soft, and reddish brown in color, as opposed to the yellow-brown hue of normal parathyroid tissue. Microscopically, a distinct mass is distinguished from a rim of uninvolved parathyroid parenchyma by a thin fibrous capsule.

    The uninvolved parathyroid tissue should have the normal parathyroid fat component and be atrophic and compressed. However, this is not always the case, and the rim of uninvolved parathyroid tissue cannot be recognized. The thin fibrous capsule is commonly broken and shrunken to the point that it cannot be distinguished.

    In addition, the tumor itself might be multinodular and irregular. Microscopically, one would expect to find a proliferation of a single cell type, which is usually the principal cell, however oxyphilic cells are frequently the dominating cell type. A combination of both types of cells can be found on occasion, raising the possibility of parathyroid hyperplasia.

    These "out of the usual" gross and microscopic aspects of parathyroid adenoma are problems that the pathologist may face on a frequent basis, and each case should be determined separately as to whether it is a real adenoma or part of parathyroid hyperplasia.

    Clinical and radiographic correlation will, of course, be useful in establishing this conclusion. Growth patterns can range from solid to pseudo-glandular, follicular, and acinar, with cystic degeneration occurring on rare occasions. Eosinophilic secretions may be present inside the follicular structures, similar to the colloid-filled follicles observed in thyroid tissue.

    There is some nuclear pleomorphism, although it is generally focal and observed in clusters. Atypical mitotic figures should not be noticed in typical parathyroid adenomas since they are inconspicuous (1/10 hpf). Delicate fibrovascular bands may be present, but thick fibrous bands should not be detected and should raise red flags for the risk of parathyroid cancer if they are. Hemorrhage, hemosiderin, inflammatory cells, and fibrosis may be seen as part of the degenerative processes, particularly in big tumors. 


    Differential Diagnosis

    A cancer is perhaps the most significant alternative diagnosis to consider when a patient arrives with hypercalcemia. 90 percent of hypercalcemia cases are caused by hyperparathyroidism and malignancy coupled. However, malignant hypercalcemia tends to appear with significantly greater ion concentrations than benign parathyroid illness.

    Another possibility is familial hypocalciuric hypercalcemia (FHH). Up to 20% of individuals with this condition will also have increased PTH levels, making distinction challenging. Patients with FHH, on the other hand, have a low urine calcium excretion and calcium/creatinine (Ca/Cr) clearance ratio, which is not seen in parathyroid adenomas.

    Thiazide diuretics and lithium are two drugs that might produce increased calcium levels. Any patient presenting with high calcium should have their medication history reviewed for any of these medicines.



    Untreated parathyroid adenoma might lead to hypercalcemia consequences. A parathyroid crisis is a rare clinical event characterized by exceptionally high calcium levels, generally greater than 15 mg/dL. Changes in mental state can lead to nervous system breakdown and coma.

    Complications from removal of the parathyroid adenoma are also possible. Injury to the recurrent laryngeal nerve is a significant complication of endocrine surgery that can result in hoarseness (unilateral injury) or airway obstruction (bilateral damage). Damage to the nerve can occur as a result of direct trauma such as cutting, grabbing, or stretching. Skeletonization, heat injury, and compression are all examples of indirect nerve damage.

    In situations of compression or stretching, the damage may be transitory and resolve in 4 to 6 weeks. If no improvement in function is apparent after 6 to 12 months, the damage should be considered permanent. If the damage is discovered during the procedure, urgent primary repair or grafting should be undertaken. 



    The majority of individuals with a parathyroid adenoma have hypercalcemia as well as bone discomfort, melancholy, and stomach pain. The presence of hypercalcemia in the blood is frequently used to make the diagnosis, which is then followed by a neck imaging test. If the problem is not detected, the morbidity is quite high. As a result, an interdisciplinary approach is advised. To make the diagnosis, a streamlined strategy involving a radiologist, endocrinologist, surgeon, and internist is required.

    The pharmacist and nurse play a vital role following surgery. The nurse must be well informed of hypocalcemia symptoms, which frequently develop during the first 24 to 72 hours after surgery. The other two consequences that a nurse should be aware of are hoarseness caused by recurrent laryngeal nerve damage and a hematoma around the neck caused by hemorrhage.

    The latter necessitates an emergency contact to the surgeon for blood evacuation, as any delay might result in respiratory arrest. The pharmacist is involved in the treatment of hypocalcemia by the use of oral supplements or intravenous calcium gluconate. The pharmacist must educate the patient on the necessity of calcium compliance; otherwise, substantial bone atrophy can occur. These interprofessional interactions show how to get the best possible outcomes for these patients.

    The prognosis for hyperparathyroidism cure with standard bilateral neck exploration is approximately 95%, with complication rates of less than 3%. Since the introduction of minimally invasive procedures, various randomized clinical studies have been done to determine if a minimally invasive approach is as effective as a standard treatment. These studies have demonstrated that a minimally invasive method has the same cure and complication rates as standard therapy while also resulting in a shorter operational time and better aesthetic results.