Parathyroidectomy for Secondary Hyperparathyroidism

History of present illness

• a.

  Many patients with renal SHPT may be asymptomatic but may present with nonspecific symptoms, such as bone or joint pain, cutaneous itching, and fatigue. However, abnormalities may be already detectable by laboratory or radiographic studies. Patients may present with elevated serum phosphate levels, reduced vitamin D production, and low or normal serum calcium levels; as a result, PTH levels would be markedly elevated.

• b.

  What serologic parameters indicate changes in renal SHPT, and is it possible to avoid progressive PTH elevation?

  At the beginning of CKD stage III (estimated glomerular filtration rate [GFR] <60 mL/min), PTH levels start to increase. According to the recommendations of the kidney disease outcomes quality initiative (KDOQI), PTH should be kept between 150 and 300 pg/mL to avoid the complete suppression of osteoclasts and prevent adynamic bone disease ( Table 85.2 ). Current therapeutic strategies include the modification of calcium and phosphorus balance by restricting the intake of dietary calcium and phosphorus and their removal during hemodialysis as well as the administration of phosphate binders, vitamin D receptor activators (calcitriol and newer vitamin D analogues), and a calcimimetic. When PTH levels cannot be maintained within the target ranges, the surgical option should be considered so as to avoid the progression of ectopic calcification.

  TABLE 85.2

  Target Ranges for Monitoring of Secondary Hyperparathyroidism

  Stage of CKD	GFR	Corrected Calcium (mg/dL)	Phosphorus (mg/dL)	iPTH (pg/mL)	Monitoring of iPTH	Monitoring of Calcium and Phosphorus
  3	30–60	Normal limits	2.7–4.6	35–70	1 year	1 year
  4	15–29	Normal limits	2.7–4.6	70–110	3 months	3 months
  5	<15	8.4–9.5	3.5–5.5	150–300	3 months	1 month

  CKD, Chronic kidney disease; GFR, glomerular filtration rate; iPTH, intact parathyroid hormone.

• c.

  Why do PTH levels continue to increase despite dietary restriction and the administration of phosphate binders, calcimimetics, and vitamin D analogues?

  As the process of low-level secretion of extracellular Ca-stimulating PTH continues, the parathyroid glands are gradually transformed from normal glands into glands manifesting diffuse hyperplasia, then nodular hyperplasia, and finally multiple adenomas. The glandular growth/hyperplasia is hyperactive, irregular, asymmetrical, and asynchronous; this process is related to the time on dialysis until the parathyroid gland finally becomes autonomous. At that point there is no longer any response to medical treatment. This is an important part of disease progression, because even after kidney transplantation the hypersecretion of PTH and hypercalcemia can persist. This condition, called tertiary hyperparathyroidism, can jeopardize the transplant surgery and long-term viability of the transplanted kidney.

  Although PTH levels can be suppressed by continuous treatment with phosphate binders, vitamin D analogues, and/or calcimimetics, a progressive reduction in the expression of CaSRs and VDRs can occur. This can ultimately result in resistance to medical management, at which point PTX might be required.

• d.

  Which patients may benefit from PTX?

  Surgical intervention should be considered in symptomatic patients who present with bone or muscle pain, muscle weakness, irritability, pruritus, bone loss, the exacerbation of anemia due to resistance to erythropoietin, or worsening cardiomyopathy. There are patients who develop resistance or intolerance to medical therapy; they too should be considered candidates for surgical intervention.

• Patients may present with painful pink or purple firm nodules or plaques surrounded by livedo reticularis that progress to deep painful ulcers covered with black eschar; such patients must be screened for surgery immediately. Sepsis from infections in skin ulcers can cause up to 80% mortality.

  This condition is known as calciphylaxis, which may be bilateral and symmetrical, affecting the thighs, abdomen, and buttocks. It occurs in only 4% of patients undergoing surgery. Where it appears that vascular calcification is driven by PTH, calcimimetic (as cinacalcet) is the preferred treatment for the control of PTH levels, as demonstrated by the evaluation of cinacalcet hydrochloride therapy to lower cardiovascular events (EVOLVE) trial. PTX is a surgical option for controlling elevated PTH levels and has been effective in isolated cases. In patients with calciphylaxis who have received urgent surgical treatment with TPTX, median survival was significantly prolonged. However, the risks associated with surgery, especially in medically complicated patients, make this a second-line treatment following failed medical management. Calciphilaxis is more commonly observed in women, patients with diabetes mellitus, obesity, hypoalbuminemia, and/or liver cirrhosis as well as in patients taking warfarin and those with a systemic inflammation or malignant disease.

• e.

  What PTH level indicates the need for surgical intervention?

  Intact PTH levels should be higher than 500 pg/mL and refractory to medical treatment.

Past Medical History

• a.

  Most of these patients have significant worsening of the CKD; therefore the following questions must be addressed:

  • 1)

    Is this patient on dialysis? If so, how long has this been the case?

  • 2)

    What is the patient’s general state of health?

  • 3)

    Has the patient had any previous hospitalizations related to SHPT?

• b.

  Medical illness

  The following must be investigated as they may influence surgery: anemia, heart disease, hypertension, diabetes mellitus, hyperlipidemia, previous thrombosis, gastrointestinal malabsorption, and voice changes.

• c.

  Surgery

  • 1)

    Evaluation of any previous neck surgery or thyroid/parathyroid surgery is mandatory. Postoperative complications are higher and success rates lower if there was previous cervical exploration.

• d.

  Family history

  • 1)

    There are some studies showing that the loss of heterozygosity (LOH) in 3q was detected more frequently in uremic parathyroid hyperplasia in comparison with LOH in 11q13 and 1q in parathyroid adenomas and LOH in 1q and 6q in familial hyperparathyroidism. It has been reported that LOH in 11q13 and the X-chromosome is present in uremic parathyroid hyperplasia.

• e.

  Medications

  • 1)

    The use of anticoagulants or antiplatelet medication should be discontinued several days prior to surgery to reduce complications from bleeding.

  • 2)

    Prolonged diuretic (especially thiazides) or lithium use is a cause of SHPT, which can lead to hyperplasia or persistent hypercalcemia.

Head and Neck

• a.

  Inspection of the neck and thyroid gland to evaluate

  • 1)

    Symmetry, size, firmness, fixation, and associated lymph nodes as well as evidence of previous neck surgery

• b.

  Laryngoscopic evaluation

  Vocal fold function should be assessed, especially in repeat surgery or in the case of associated thyroid masses.

Patients may present with elevated serum phosphate, reduced vitamin D, and low or normal serum calcium levels and, as a result, elevated PTH levels.

The KDOQI of the National Kidney Foundation recommends the following target levels for renal SHPT patients who are on dialysis:

• a.

  Serum calcium level between 8.4 and 9.5 mg/dL

• b.

  Serum phosphate level of 3.5 to 5.5 mg/dL

• c.

  Intact PTH (iPTH) of 150 to 300 pg/mL

Although there are no specific indications for PTX listed in the KDOQI guidelines, PTX is considered in severe renal SHPT refractory to medical treatment. PTX effectively and quickly lowers calcium, PTH, and phosphorus levels and also helps to prevent cardiovascular complications and ectopic calcifications. Postoperative bone biopsy has shown suppression of bone resorption and initiation of bone formation. Up to 32% of patients with prolonged renal failure require PTX despite expensive medical treatment.

Preoperative routine evaluation includes the following:

• a.

  Ultrasonography (US) of the neck

  • 1)

    To localize the parathyroid as well as to evaluate any concomitant thyroid disease or nodules that may point to the presence of an intrathyroidal parathyroid gland ( Fig. 85.1 )

    

• b.

  Technetium-99m ( ^99m Tc) sestamibi scintigraphy with or without single-photon emission computed tomography (SPECT)

  • 2)

    This is usually not ordered but may be helpful in identifying ectopic glands and facilitating surgical planning. The combination of US and 99mTc sestamibi scintigraphy can provide more accurate results. Because hyperplasia is the predominant physiologic mechanism, the presence of ectopic glands creates surgical challenges more frequently (4 times higher) as compared with primary hyperparathyroidism.

• c.

  Four-dimensional contrast-enhanced CT (4D CT)

  • 3)

    Used mainly in preparation for reoperation to provide precise anatomic information regarding orthotopic or ectopic glands, multiglandular disease, and coexisting pathology such as thyroid nodules or lymph nodes. Disadvantages include cost and radiation exposure.

• d.

  Magnetic resonance imaging (MRI)

  • 4)

    This is helpful in the visualization of mediastinal hyperplastic parathyroid glands. Abnormal glands, identified on adipose tissue–saturated T2-weighted (hyperintense) imaging, can be distinguished from the surrounding mediastinal adipose tissue using this modality, and gadolinium may help to enhance the abnormal glands. MRI is not as helpful in visualizing cervical glands.

• e.

  C-methionine positron emission tomography and computed tomography (PET CT) or 18 fluorodeoxyglucose (FDG) PET CT—or even selective venous catheterization with PTH assessment—appear to be reserved for special indications such as reoperation.

Severe renal SHPT

• a.

  Hyperphosphatemia refractory to medical management with PTH levels exceeding 800 pg/mL or extraosseous calcifications with PTH greater than 500 pg/mL as well as severe radiologically or histologically proven osteopathy

Calciphylaxis

Intractable pruritus

Symptomatic patients or patient’s preference

Nodular hyperplastic parathyroid

High-risk medical comorbidities

Pre-existing recurrent nerve paralysis

Previous neck surgery or explorations constitute a relative contraindication; surgery in this setting should be performed only by experts in parathyroid surgery.

Dialysis patients should undergo dialysis 12 to 24 hours or at the latest 36 hours prior to surgery so as to minimize the administration of heparin.

Cardiologic evaluation is desirable because renal SHPT patients (around 80%) frequently have coexisting hypertension, diabetes, and cardiac disease.

Electrolyte abnormalities should be corrected as much as possible. Be aware of hypocalcemia, hyperphosphatemia (main cause of pruritus), hypermagnesemia, and hyperkalemia. The consequences of hypermagnesemia include hypoventilation, central nervous system (CNS) depression, hypotension, and shock. Hyperkalemia is an important electrolyte disorder to consider in contemplating general anesthesia and the potential use of muscle relaxants, which may increase serum calcium and result in various cardiac arrhythmias. Electrocardiography (ECG) in hyperkalemic patients can show a high T wave, extended P-R interval, and widened QRS complex. Elective surgery is ideally performed with a potassium value below 5.5 mEq/L.

Anticoagulant medications should be discontinued if possible.

All tissue removed at previous surgeries should be acquired and reviewed by in-house experts.