Parathyroid Gland

Primary Hyperparathyroidism (PHPT)

1. Epidemiology
• most common cause of hypercalcemia
• female-to-male ratio is 3:1
• most cases are in postmenopausal women


2. Etiology
• unknown at present
• risk factors include head and neck irradiation in childhood, MEN1 and MEN2a
• pathologies include a single adenoma (85%), multiple adenomas (4%), or four-gland hyperplasia (10%)


3. Clinical Manifestations
• prior to the advent of routine measurement of serum calcium, the most common symptoms of PHPT were renal stones (64%), bone disease (20%), peptic ulcer disease (12%) and hypertension (4%)
• ‘stones, bones, and abdominal groans’
• there are many other nonspecific regional symptoms of hypercalcemia
• constitutional: fatigue, weight loss, anorexia
• neurologic: headache, memory loss, neurosis, psychosis
• GI: peptic ulcer disease, pancreatitis, nausea, vomiting, constipation
• cardiovascular: hypertension, heart block
• renal: stones, hematuria, flank pain, polyuria, nocturia
• musculoskeletal: muscle, joint, bone pain; weakness
• dermatologic: pruritus, brittle nails
• today, more than 80% of patients diagnosed with primary hyperparathyroidism are ‘asymptomatic’ or have mild constitutional symptoms such as muscle fatigue and weakness
• the classic radiologic finding of osteitis fibrosis cystica with subperiosteal bone resorption is now rarely seen


4. Diagnosis
• most of the causes of hypercalcemia can be ruled out by a careful history and physical
• PHPT requires an elevated serum calcium along with an elevated or inappropriately normal PTH level
• hypophosphatemia is also usually present
• vitamin D deficiency will cause a compensatory rise in serum calcium and PTH, and must be ruled out
• familial hypocalciuric hypercalcemia is the condition most difficult to distinguish from primary hyperparathyroidism


1. Familial Hypocalciuric Hypercalcemia (FHH)
• characterized by hypercalcemia, hypocalciuria, and normal or low PTH levels
• results from a loss of function mutation in the calcium sensing receptor gene
• a 24 hr urine collection for calcium may be necessary to differentiate FHH from hyperparathyroidism
• a value < 100 mg/24 hr is suspicious for PHPT and should be confirmed with a calcium/creatinine clearance ratio


5. Indications for Parathyroidectomy
• serum calcium > 1 mg/dL above the upper limit of normal
• urinary calcium excretion > 400 mg/24 hr
• asymptomatic patients < 50 years old
• overt symptoms
• markedly reduced bone density (T score < 2.5 at any site)
• vertebral compression fractures, fragility fractures, osteoporosis
• reduced creatinine clearance in the absence of other causes, nephrolithiasis


6. Preoperative Preparation
1. Hypercalcemic Crisis
• rare in PHPT
• life-threatening condition when serum calcium level is greater than 14 mg/dL
• volume resuscitation with 0.9 NS is the cornerstone of therapy
• calcitonin will rapidly lower serum calcium levels
• once urine output is adequate, a loop diuretic can be used to stimulate a calciuresis
• bisphosphonates inhibit osteoclast bone resorption, but they take severl days to have an effect


2. Localization Studies
• preoperative localization identifies patients who are candidates for minimally invasive parathyroidectomy
• the most common localization studies are neck US and sestamibi scanning
• the use of both studies together improves identification and surgical success compared with each test alone


1. Neck Ultrasound
• sensitivity for detecting abnormal parathyroid glands ranges from 76% - 79%
• specificity is 96%
• normal glands are not visualized
• a parathyroid adenoma appears as a hypoechoic mass near the thyroid gland
• can also detect concurrent thyroid pathology
• cannot detect mediastinal parathyroids



2. Sestamibi Scanning
• technetium 99m sestamibi scan has an affinity for abnormal parathyroid tissue
• adding single photon emission computed tomography (SPECT) allows 3-d imaging
• particularly valuable in identifying ectopic parathyroid adenomas
• sensitivity for identifying a single adenoma is 80% to 90%
• sensitivity is diminished in multigland disease or thyroid disease



7. Parathyroidectomy
1. Bilateral Neck Exploration
• classic approach
• required for patients with nonlocalizing preoperative imaging or multigland disease
• one thyroid lobe is mobilized medially and anteriorly by dividing the middle thyroid vein
• the recurrent laryngeal nerve and inferior thyroid artery are identified and protected
• all parathyroid tissue is identified on one side of the neck, and then the procedure is repeated on the other side
• no parathyroid tissue is removed, normal or abnormal, until the anatomy and pathology have been clarified bilaterally
• the operating surgeon, not the pathologist, determines whether the patient has an adenoma or multigland hyperplasia
• if no abnormal parathyroid tissue is found, identifying all the normal glands will help direct the search for the missing gland
• if an inferior gland is missing, then the thyrothymic ligament and cervical thymus should be explored
• inferior glands may also be in a subcapsular location with respect to the thyroid gland - a true intrathyroidal parathyroid gland is extremely rare
• if a superior gland is missing, it is often found in a position posterior to the inferior glands
• superior glands may be found in the tracheoesophageal groove, carotid sheath, behind the larynx or trachea, or in the posterior mediastinum
• if the adenoma cannot be found then the procedure should be terminated, and the patient reevaluated
• occasionally the blood supply to the missing gland will be divided during the dissection and the patient will be normocalcemic postop
• a formal mediastinal exploration (sternotomy) should not be performed at the initial operation


2. Minimally Invasive Parathyroid Exploration
• patients who have a solitary adenoma localized preop are candidates for a focused parathyroidectomy
• need to have available an intraoperative PTH assay
• in the operating room a baseline PTH is drawn
• a small neck incision is then made, guided by the sestamibi scan or US
• the goal is to identify the single adenoma and remove it
• after the abnormal gland is removed, a postresection PTH assay is performed 10 minutes later
• the procedure is terminated if the PTH falls 50% from baseline (Miami criterion)
• if the PTH remains > 50% above baseline, additional samples are drawn
• if the PTH still remains > 50% above baseline, the exploration is continued either on the ipsilateral or contralateral side of the neck
• general anesthesia is not required in every case


3. Management of Multigland Disease
1. Subtotal Parathyroidectomy
• if all 4 glands are enlarged, resection of 3½ glands is the preferred procedure
• leaving the remnant in situ has a higher incidence of parathyroid viability and a decreased incidence of permanent hypoparathyroidism when compared with total parathyroidectomy and autotransplantation
• the most normal appearing gland is the one that should be divided
• the remnant should be marked with a clip or a suture to facilitate identification if reoperation is required
• in familial disease, the cervical thymus should also be resected since the incidence of supernumerary glands is higher, particularly in MEN-I


2. Total Parathyroidectomy and Autotransplantation
• multiple minced 1 mm fragments of parathyroid tissue are placed in the nondominant brachioradialis muscle of the forearm
• additional parathyroid tissue can be cryopreserved in case of graft failure
• advantage of this procedure is that if recurrent hyperparathyroidism occurs, treatment requires only removing some of the grafts under a local anesthetic and a redo neck exploration is avoided
• graft-dependent hyperparathyroidism can be diagnosed by demonstrating a gradient in PTH levels between both arms
• grafts may also be imaged using sestamibi


4. Complications
• temporary hypocalcemia is common because the remaining parathyroid tissue has been chronically suppressed
• postoperative calcium and vitamin D should be given until the remaining glands regain function
• permanent hypoparathyroidism is very rare after adenoma excision


5. Persistent Hyperparathyroidism
• primary reason is an ‘improperly performed primary operation’ - most missed glands are found in the neck
• first step is to reconfirm the diagnosis (r/o FHH, vitamin D deficiency)
• localizing studies are mandatory (sestamibi scan, ultrasound, ultrasound-guided fine-needle biopsy, CT, MRI, selective internal jugular venous sampling)
• review previous operative notes and pathology reports
• if all localizing studies are negative, blind exploration should not be performed
• reoperative cure rates are 10% to 20% lower (80% - 90%)
• postoperative complications are 3 to 5 times higher