Postoperative Hypoparathyroidism: Medical and Surgical Therapeutic Options

Abstract

Background:

Hypoparathyroidism occurs when the parathyroid glands, through lack of secretion of or resistance to parathyroid hormone (PTH), are unable to maintain calcium homeostasis. Transient and permanent hypoparathyroidism are most commonly seen as complications of neck surgery, resulting from devascularization of the parathyroids, unintentional resection, or accidental coagulation of the parathyroids.

Summary:

Although strategies for treatment of transient and permanent hypoparathyroidism differ, the classical approach involves supplementation with calcium and vitamin D or its analogues with the major goal of achieving low normal serum calcium and normal serum phosphorus. There are a variety of calcium and vitamin D preparations available for use in the treatment of symptomatic hypoparathyroidism. In selecting the appropriate vitamin D sterol for treatment, it is important to consider the pharmocodynamics, the potency at the tissue level, the rapidity of action, and ease of reversal of toxicity. Drawbacks to conventional therapy, including narrow therapeutic window and propensity for hypercalciuria and hypercalcemia, have prompted investigation into alternatives, namely PTH replacement and parathyroid gland autotransplantation.

Conclusion:

Long-term supplementation with vitamin D or its analogues and oral calcium is the mainstay of management of postoperative hypoparathyroidism; however, PTH replacement strategies with either PTH or parathyroid gland autotransplantation are emerging as alternative strategies to avoid the complications of conventional therapy.

Introduction

H ypoparathyroidism occurs when the parathyroid glands are unable to maintain calcium homeostasis. The differential diagnosis of hypoparathyroidism is wide and includes autoimmune or surgical destruction of parathyroid tissue, reversible impairment of parathyroid hormone (PTH) secretion, genetic disorders of parathyroid gland development, and PTH resistance. It is most commonly seen as a complication of surgery, specifically thyroidectomy, parathyroidectomy, or radical neck surgery. Thyroidectomy is the usual treatment for medullary thyroid cancer and differentiated thyroid cancer, which includes follicular and papillary cancer and accounts for more than 90% of all thyroid cancer (1). Central neck dissection, initially introduced in the treatment of medullary thyroid cancer to minimize local recurrences and attain a higher rate of biochemical cure, is now becoming more widely used in the management of papillary thyroid cancer (2). There are limited data to suggest that systematic compartment oriented central lymph node dissection may decrease the recurrence of papillary thyroid cancer and may improve disease-specific survival (1,2). The central neck compartment involved in dissection commonly contains the inferior parathyroids (2). Therefore, there may be a higher rate of permanent hypoparathyroidism when central lymph node dissection is performed with total thyroidectomy; in a review of prospective cohort studies, retrospective studies and case series, rates of permanent hypoparathyroidism ranged from 1.4% to 14.3% in those who underwent central lymph node dissection compared to 0–0.5% in those who did not (1,2). Postoperative hypoparathyroidism is likely due to devascularization of the parathyroids, unintentional resection, or accidental coagulation by heat induction. The increased morbidity with central lymph node dissection may be attributed to operator expertise, the number of lymph nodes resected, and concurrent thymectomy, as well as incidental parathyroidectomy (1 –3). In addition, thyroid conditions such as Graves' disease, thyrotoxicosis secondary to hyperactive thyroid adenomas, recurrent goiter, thyroid carcinoma, substernal goiter, and re-operation of the thyroid are associated with increased risk of developing postoperative hypoparathyroidism (4,5). Significant damage to the parathyroids must occur before hypoparathyroidism develops, given the ample parathyroid secretory reserve.

Postsurgical hypoparathyroidism may be transient or permanent, defined by most studies as insufficient PTH to maintain normocalcemia 6 months after surgery. In a multicenter study of 14,934 patients undergoing thyroid surgery (total lobectomy, total thyroidectomy, subtotal thyroidectomy with monolateral or bilateral remnants), persistent hypoparathyroidism, defined as hypocalcemia persisting longer than 1 year, occurred after 1.7% of all the operations. Temporary hypoparathyroidism was noted in 8.3% of cases. Symptomatic hypocalcemia accounted for 63% of all surgical complications (6). In reviewing a Scandinavian database of thyroid surgeries, Bergenfelz et al. (7) found that of 1,648 patients undergoing bilateral thyroid surgery, 105 (6.4%) were treated with intravenous (IV) calcium for significant hypocalcemia. At the first postoperative follow-up (1‱6 weeks post surgery), 128 patients (7.8%) were receiving fixed-dose calcium, 43 (2.6%) were treated with a vitamin D analogue, and 121 (7.3%) were treated with both oral calcium and vitamin D analogue therapy (7). After 6 months, 27 patients (1.6%) continued treatment with oral calcium alone; 73 patients (4.4%) remained on vitamin D analogue therapy, and of those, 50 were also taking oral calcium (7).

Physiologic Action of PTH

The parathyroid glands, via the action of PTH, are responsible for regulating extracellular fluid calcium and bone and mineral metabolism (8). The parathyroid glands detect serum calcium concentrations through a calcium-sensing receptor present on the surface of the parathyroid cells. When serum calcium concentrations are low or falling, the parathyroid glands are stimulated within seconds to secrete PTH. Hypocalcemia also acts to increase the levels of PTH messenger RNA (mRNA) and to stimulate parathyroid cell growth, thereby regulating PTH secretion over a period of hours and days, respectively (8). Once secreted, PTH, an 84 amino acid peptide, enters the circulation and binds to the type 1 PTH receptor in the bone and kidney (8). In bone, PTH causes bone resorption and liberation of calcium and phosphorus into the circulation. In the kidney, PTH acts on the proximal and distal tubules to increase calcium reabsorption and promote phosphorus excretion. An additional action of PTH in the kidney is to induce the enzyme (CYP27B1) that converts 25 hydroxyvitamin D to 1,25 dihydroxyvitamin D, the biologically active form of vitamin D that increases intestinal calcium and phosphorus absorption. In concert, these actions restore ionized calcium levels to the normal range.

Clinical Manifestations of Hypoparathyroidism

Insufficient secretion or action of PTH manifests as symptomatic hypocalcemia with neuromuscular symptoms, such as muscle cramping, twitching, and spasm, circumoral and acral numbness and paresthesias, laryngospasm, and bronchospasm (8,9). Cardiac function may be affected with resultant prolonged QT interval corrected for heart rate (QT_c), and in rare cases, depressed systolic function. In the acute postoperative course, symptomatic hypocalcemia may present dramatically with tetany, seizures, altered mental status, refractory congestive heart failure, or stridor. Patients with permanent postsurgical hypoparathyroidism (duration of disease greater than 8‱10 years) may develop basal ganglia calcifications or cataracts (3,9). Permanent hypoparathyroidism is also associated with elevated bone mineral density although it is unclear if this increase in bone density confers fracture protection (3,10).

Initial evaluation with physical exam should assess for neuromuscular excitability; patients who do not display overt muscle spasms or twitching may have underlying neuromuscular irritability that can be provoked with Chvostek's or Trousseau's sign (9,11). Chvostek's sign is produced by tapping on the facial nerve as it exits the parotid gland, an area about 0.5 cm inferior to the zygomatic process and 2 cm anterior to the earlobe. A positive sign ranges from twitching of the ipsilateral upper lip to spasm of all facial muscles. Chvostek's sign can be elicited in 10% of normal people and was absent in 29% of patients in a small study of patients with hypoparathyroidism and hypocalcemia (11). However, Trousseau's sign is considered to be more sensitive and specific for hypocalcemia, with 94% of hypocalcemic patients manifesting a positive response compared to 1% of normocalcemic patients (11). Trousseau's sign is elicited by inflating a sphygmomanometer placed on the upper arm 20 mm Hg above the systolic blood pressure for 3 minutes. Painful carpal spasm with wrist flexion, thumb flexion, and finger hyperextension is a positive response (9,11,12).

Laboratory testing reveals normal or inappropriately low intact PTH level with concurrent low serum albumin–corrected total calcium or ionized calcium values. In general, serum phosphorus levels are elevated or high normal (9). Serum concentrations of 1,25-dihydroxyvitamin D are usually low or low normal. Urinary calcium levels in a 24-hour collection may also be low (9).

Several studies aimed at determining predictors of significant postoperative hypocalcemia requiring therapeutic intervention have been conducted, looking specifically at perioperative serum PTH levels and postoperative serum calcium levels (12 –15). Nahas et al. (12) completed a retrospective chart review of 135 patients undergoing total or completion thyroidectomy and determined that patients with a positive slope between serum calcium levels measured 6 and 12 hours postoperatively were safe to discharge within 24 hours after surgery with or without calcium supplementation (12). Soon et al. (14) investigated the usefulness of measuring early postoperative PTH levels for predicting hypocalcemia and found that serum PTH <1 pmol/L (9 pg/mL) 1 hour after total thyroidectomy predicted the development of hypocalcemic symptoms with a sensitivity of 92.3% and a specificity of 78.8%. Other investigators have found that a PTH level <15 pg/mL on the first postoperative day combined with a serum calcium level <1.9 mmol/L (7.6 mg/dL) on the second postoperative day predicted transient or permanent hypoparathyroidism with a sensitivity of 96.3%, a specificity of 96.1%, a positive predictive value of 86%, and a negative predictive value of 99.0% (16).

Treatment and General Approach

In treating hypoparathyroidism, the goal is to control symptoms while minimizing the complications of treatment, aiming for a low-normal serum calcium and normal phosphorus by supplementing calcium and vitamin D or its analogues. Treating patients with hypocalcemia requires consideration of their symptoms, specifically the type and severity of symptoms, as well as the serum calcium level, and may require IV calcium until an oral calcium regimen can be established (9). Long-term treatment with calcium and vitamin D does not restore physiologic calcium homeostasis and often results in hypercalciuria even in the face of normocalcemia, thereby increasing the risk of renal sequellae (3). Therefore, drugs that increase renal tubular reabsorption of calcium, such as thiazide diuretics, have been added as ancillary agents to the classical treatment regimen. Phosphate binders have also been used as an adjunct to conventional therapy to address the hyperphosphatemia that can be seen as a part of the disordered calcium/phosphorus homeostasis.

Calcium

In the immediate postoperative period, patients should be monitored with serial physical exams and serial measurements of serum calcium, beginning about 6 hours after surgery (12,16,17). In patients with signs or symptoms of hypocalcemia and total calcium <7 mg/dL, IV calcium supplementation is warranted; in these instances, patients may not be able to tolerate oral therapy and such therapy would have a slower onset of action than IV supplementation (17). In addition to IV calcium, some investigators recommend concurrent initiation of oral calcium and 1,25-dihydroxyvitamin D therapy when hypocalcemic symptoms are present or if serum calcium 12 hours postoperatively is <8 mg/dL regardless of symptoms (12). In patients warranting IV calcium therapy, calcium gluconate is preferred to calcium chloride, as there is less risk of tissue necrosis if extravasation occurs. A dose of 1 g (93 mg of elemental calcium) or 2 g infused slowly, over a period of 10 minutes, with electrocardiographic and clinical monitoring is indicated (11,18,19). Since the effects of a bolus of IV calcium decline after 2 hours, continuing hypocalcemia may be managed with an infusion of calcium gluconate or calcium chloride (through a central vein) over several hours. Begin infusing calcium gluconate (10 g of calcium gluconate in 1 liter of 5% dextrose) at a rate of 1–3 mg of elemental calcium/kg of body weight/hr, which will increase serum calcium by 0.5–0.75 mM (2‱3 mg/dL) (20). Once IV calcium therapy is initiated, serial serum ionized calcium levels should be obtained every 1–2 hours in order to adjust the infusion rate with a goal of symptom resolution and stable ionized calcium >1 mmol/L (4 mg/dL) (9). Thereafter, serum ionized calcium can be measured every 4 to 6 hours while the calcium infusion is tapered off slowly over 24–48 hours or longer while an oral regimen of calcium and vitamin D is started (9).

The alternative to IV calcium therapy for postoperative patients with symptomatic hypocalcemia or low serum calcium with or without symptoms (<2 mmol/L, 8 mg/dL) involves oral calcium and vitamin D supplementation. Specifically, Soon et al. (14) administered Caltrate (calcium carbonate, Wyeth, Madison, NJ) 600 mg (elemental calcium content) twice daily to 1200 mg four times daily to patients and began calcitriol (Rocaltrol, Roche Pharmaceuticals, Natley, NJ) 0.25 μg twice daily to 0.5 μg four times daily if serum calcium did not respond within 24 hours. Calcium carbonate, calcium lactate, calcium citrate, calcium glubionate, and calcium gluconate are all available oral supplemental forms. These forms contain variable amounts of elemental calcium, with calcium carbonate containing the most at 40% and calcium glubionate the least at 6.6%. Calcium citrate, lactate, and gluconate contain 21%, 13%, and 9%, respectively. Calcium carbonate requires an acidic environment for absorption and thus must be taken with meals and may be less effective in individuals taking proton pump inhibitors and H2 blockers. Calcium citrate and calcium glubionate do not require an acidic environment for absorption (9). Start with a dose of 500 to 1000 mg of elemental calcium (three times a day) and adjust the dose to control symptoms and reach the desired level of calcium, 8–8.5 mg/dL. Usually 1 to 2 g of elemental calcium (three times daily) is needed and more frequent dosing may be required (9).

After discharge and within 1–3 weeks on calcium supplementation, outpatient evaluation of serum calcium and phosphorus is necessary for appropriate titration of oral substitution therapy (13). Follow-up once every 3 months thereafter is reasonable and should continue until serum calcium normalizes after withdrawal of supplemental therapy with calcium and vitamin D for about 1 week (13,16).

Vitamin D

Vitamin D and its analogues are mainstays in the treatment of hypoparathyroidism. There are a variety of vitamin D preparations available, including ergocalciferol (vitamin D₂), cholecalciferol (vitamin D₃), alphacalcidol (1αOH-vitamin D₃), dihydrotachysterol, and calcitriol (1,25-dihydroxy vitamin D₃). The biologically active form of vitamin D is 1,25-dihydroxyvitamin D, which maintains serum calcium within the normal range, by increasing the efficiency of absorption of intestinal calcium and phosphorus. Only 10–15% of dietary calcium and about 60% of dietary phosphorus are absorbed in the absence of vitamin D; 1,25-dihydroxyvitamin D works to increase the efficiency of calcium absorption from the small intestine to 30–40% and phosphorus absorption to about 80% (21). In addition, 1,25-dihydroxyvitamin D promotes bone resorption as a source of calcium. 1,25-dihydroxyvitamin D causes increased expression of the receptor activator of nuclear factor kappa beta ligand (RANKL) by osteoblasts, which is then bound by its receptor RANK on preosteoclasts, inducing preosteoclasts to become mature osteoclasts. Mature osteoclasts mobilize calcium and phosphorus from the bone, maintaining blood levels of calcium and phosphorus (21).

However, in hypoparathyroidism, there is a defect in the production of 1,25-dihydroxyvitamin D via 1-alphahydroxylation of 25-hydroxyvitamin D in the kidney, due to the absence of the direct action of PTH on the 1-alphahydroxylase (CYP27B1) promoter (8,22 –25). Decreased 1-alphahydroxylation and the resultant diminished production of 1,25-dihydroxyvitamin D ultimately manifests as symptomatic hypocalcemia requiring treatment.

In selecting a vitamin D sterol for treatment, it is important to consider the pharmocodynamics of the drug, its molecular potency at tissue level, its rapidity of action, and ease of reversal of toxicity (Table 1).

Table 1.

Treatment of Hypoparathyroidism

Medication	Dose
Calcium carbonate
Os-Cala	1.25 g tablet (500 mg of elemental calcium), 1.5 g tablet (600 mg)
Tumsa	Regular 500 mg tablet (200 mg of elemental calcium), E–X 750 mg tablet (300 mg), Ultra 1000 mg tablet (400 mg)
Caltratea	1.5 g tablet (600 mg of elemental calcium)
Calcium citrate
Citracala	950 mg tablet (200 mg of elemental calcium), 1.2 g tablet (250 mg), 1.5 g tablet (315 mg)

Vitamin D analogues		Cost for 30 days of therapy b
Ergocalciferol (Vitamin D₂)	25,000–100,000 IU/day	50,000 IU (1.25 mg) capsules (#30)–$48.17
Cholecalciferol (Vitamin D₃)	50,000–200,000 IU/day	50,000 IU (1.25 mg) capsules (#30)–$8.70
Dihydrotachysterol	0.2–1.0 mg/day	0.125 mg tabs (#60)–$225.59
Alphacalcidiol (1αOH-vitamin D₃)	0.5–3.0 μg/day	0.25 μg tabs (#60)–$27.00
Calcitriol (1,25 dihydroxy D₃)	0.5–3.0 μg/day	0.5 μg tabs (#30)–$55.99

Os-Cal (GlaxoSmithKline, Brentford, United Kingdom); Tums (GlaxoSmithKline, Brentford, United Kingdom); Caltrate (Wyeth, Madison, NJ); Citracal (Bayer Healthcare, Leverkusen, Germany).

Prices obtained from drugstore.com, amazon.com, alfacalcidol.net, Walgreens.com.

Ergocalciferol/Cholecalciferol

Ergocalciferol is available as an over-the-counter supplement and through prescription. Cholecalciferol is available in over-the-counter supplements and is three times as potent as ergocalciferol. Both preparations effectively achieve the therapeutic goal of normal or low normal serum calcium levels and are inexpensive, though supraphysiologic doses of ergocalciferol and cholecalciferol may be necessary to overcome the rigid steric constraint of skeletal and intestinal receptor sites to 1,25-dihydroxyvitamin D (26). Start 50,000 to 100,000 IU/d as soon as tetany is controlled by IV calcium. Check serum calcium, albumin, phosphorus, and creatinine 2 weeks after the initial dosing to adjust the dose for a goal serum albumin corrected calcium 8–8.5 mg/dL. The usual therapeutic dose of ergocalciferol for hypoparathyroidism is 25,000 to 100,000 IU/d (23). The time of onset of action is 10 to 14 days and the effect persists for 14 to 75 days (11,18,19,22,23,27).

Dihydrotachysterol

Dihydrotachysterol is a chemical reduction product of tachysterol first isolated in 1930 in an attempt to discover a sterol more active than vitamin D (28). It contains an 1-alpha hydroxyl functional group and thus does not require renal hydroxylation (28,29). Following oral administration of dihydrotachysterol, intestinal calcium absorption increases, causing a rise in serum calcium within several hours; and with daily administration, the onset of action is in 4 to 7 days and the effect lasts for 7 to 21 days (11,18,19,29). Begin with 0.2 mg daily and check the serum calcium in several days. The usual dose required to achieve normocalcemia is 0.2–1 mg/d, and the average daily dose is 0.6 mg/d (9). Dihydrotachysterol, although used frequently in the past, has fallen out of favor with the development of more specific vitamin D analogues.

Alphacalcidol

Alphacalcidol is the synthetic analogue of cholecalciferol which requires conversion in the liver to 1,25-dihydroxyvitamin D before initiating a biological response (27). Once active, alphacalcidol potentiates intestinal calcium absorption in 1–2 days and lasts for 5–7 days (9,23,27). Start with a dose of 1 μg/day. Measure serum calcium weekly and increase the dose by 0.25–0.5 μg/d to maintain a low normal to normal serum albumin corrected calcium (8‱8.5 mg/dL). Only small doses of alphacalcidol, 0.5–3 μg/d, are needed to rapidly increase serum calcium and improve symptoms (23,24,27). Alphacalcidol is similar to calcitriol in potency and clinical effectiveness (28).

Calcitriol

Calcitriol is the most active form of vitamin D at the vitamin D receptor in vivo (9). It does not require hydroxylation in the liver or kidney, and thereby bypasses the relative defect in 1-alphahydroxylation present in hypoparathyroidism. Given the increased potency of 1-alphahydroxylated forms of vitamin D, only 0.25 to 1 μg once or twice daily are needed to correct hypocalcemia and improve symptoms in patients with hypoparathyroidism (9,24). Start with a dose of 0.25 μg/day. In the acute setting, this dose may require rapid titration in order to achieve a low normal to normal serum albumin corrected calcium (8‱8.5 mg/dL) as levels are checked every 4 to 6 hrs; doses range from 0.25 μg to 1 μg once to twice daily. When an optimal dose is determined, check serum calcium every 2 to 4 weeks. Once administered, calcitriol rapidly acts to increase intestinal calcium absorption over 2 hours (23 –25,29). Its maximal effect occurs at about 10 hours after administration and it endures for 2–3 days (9,29). Comparing the cost of a 30-day supply to the usual daily dose of the various vitamin D analogues, calcitriol and alphacalcidiol are more expensive than cholecalciferol and ergocalciferol (see Table 1).

Monitoring

Treatment with any of the vitamin D sterols carries the risk of vitamin D intoxication, presenting with hypercalcemia, hypercalciuria, and hyperphosphatemia. Hypercalcemia may occur with any vitamin D analogue but the timing of when hypercalcemia emerges depends on the half-life of the analogue, ranging from days to several months. Thus, monitoring for complications of therapy is critical. Symptomatic hypercalcemia may manifest as gastrointestinal disturbance with constipation, dyspepsia, nausea, and vomiting; change in mental status ranging from fatigue to coma; soft tissue calcification; or renal damage. Hypercalcemia due to long-term treatment with dihydrotachysterol may take 3–14 days to resolve (28,29). Alphacalcidiol induced hypercalcemia can take 5–10 days to resolve (28). The risk of hypercalcemia is increased due to the potency of calcitriol, but its shorter half life ensures quicker resolution of toxicity, in 2–10 days (28).

Hypercalciuria is also a known effect of vitamin D therapy, due to the increased load of calcium filtered by the kidney in the setting of poor renal calcium reabsorption (8,27). Persistent hypercalciuria can occur even with normal or low normal serum calcium (3). Thiazide diuretics may be used to reduce or prevent hypercalciuria; once the 24-hour urinary calcium reaches 300 mg, a thiazide diuretic coupled with a low salt diet should be initiated (30).

Increased intestinal phosphate absorption occurs with vitamin D therapy and leads to hyperphosphatemia, especially in the face of decreased urinary phosphate excretion. When the product of the serum calcium and phosphate, both expressed in milligrams per deciliter, is greater than 55 the risk of precipitation of calcium-phosphate salts in soft tissues, such as the lens, basal ganglia, and kidney, is high (9). Hyperphosphatemia can be treated by prescribing a low phosphorus diet and by adding phosphate binders to maintain an acceptable calcium-phosphate product.

Routine monitoring of serum calcium, phosphorus, and creatinine should occur within at least 1–3 weeks postoperatively and may be continued as frequently as weekly to monthly during initial dose adjustments of oral calcium and vitamin D supplementation (9,13). Once a stable regimen is established, follow-up with serum calcium, phosphorus, and creatinine should continue once every 3 months until serum calcium normalizes with cessation of oral supplements for 1 week (13). In those with permanent hypoparathyroidism, in addition to serum measurements, urinary calcium and creatinine levels are measured twice yearly to detect renal toxic effects of hypercalciuria (9). The goals of therapy are to control symptoms and to maintain a low normal to normal serum albumin corrected calcium (8‱8.5mg/dL), a calcium-phosphate product below 55, and a 24-hour urinary calcium below 300 mg (9). Monitoring for cataract development should be done yearly with slit lamp and ophthalmoscopic examinations (9). When concerned about vitamin D intoxication an elevated 25-hydroxyvitamin D level is an indicator of hypervitaminosis D (29).

PTH Replacement

In a recent study of well-being, mood, and mineral ion homeostasis in women treated with vitamin D and calcium for postsurgical hypoparathyroidism scores for anxiety, phobic anxiety, depression, and somatization were higher than among age- and sex-matched controls with intact function after thyroidectomy (3). These data suggest that quality of life may be compromised in patients with hypoparathyroidism even with treatment to optimize biochemical values (3). Drawbacks such as these have prompted investigation into alternatives to calcium and vitamin D therapy, specifically PTH replacement therapy.

Only a few small randomized trials have evaluated the use of injectable synthetic human PTH (1-34) in patients with hypoparathyroidism. In a 3-year trial comparing PTH (1-34) with calcitriol, both given every 12 hours with supplemental calcium, both treatments maintained the serum calcium within or just below the normal range (7.6‱8.8 mg/dL or 1.9‱2.2 mmol/L), but the PTH regimen resulted in less urinary calcium excretion (10,31). Although urine calcium decreased with PTH therapy, there was no significant improvement in renal function. Treatment with PTH (1-34) produced a significant increase in markers of bone turnover, although there were no significant differences in bone mineral density between the groups (10,31). A recent trial in children showed that twice-daily PTH (1-34) provides more effective treatment of hypoparathyroidism compared with once-daily treatment as it reduces the variation in serum calcium at a lower total daily PTH (1-34) dose (32). Further studies are needed to determine the long-term efficacy and skeletal effects of PTH in both children and adults. Trials of the use of recombinant human PTH for transient postoperative hypocalcemia are ongoing. Currently, PTH (1-34) is not approved by the U.S. Food and Drug Administration for use in hypoparathyroidism.

Parathyroid Autotransplantation

Parathyroid gland autotransplantation should be considered when there is a high likelihood of postoperative hypoparathyroidism as in the case of Graves' disease, substernal goiter, thyroid malignancy, or thyroid re-operation (8,16,33 –35), The technique of parathyroid autotransplantation varies with different centers and preparation of the parathyroid tissue ranges from thin sectioning and mincing, to homogenization into a paste form (33). Olson et al. (34) found in their retrospective study of 194 patients undergoing thyroidectomy that 54% experienced transient hypocalcemia but only 1% became permanently hypoparathyroid. They attribute this success to an autotransplantation protocol that required parathyroid glands found within the resected thyroid or any glands of questionable viability be stored in iced saline for <120 minutes, sliced, and then 20 pieces grafted into the sternocleidomastoid muscle. In a prospective study of 5846 patients undergoing bilateral thyroid surgery, parathyroid autografting was performed in 120 patients with no cases of subsequent permanent hypoparathyroidism (4). Similar experiences were reported by Lo and Lam (33), demonstrating that routine parathyroid autotransplantation of one to two parathyroid glands during thyroidectomy nearly eliminates postoperative hypoparathyroidism.

Conclusion

Postsurgical hypoparathyroidism occurs as a result of parathyroid gland injury or resection and may be transient or permanent. It may manifest as symptomatic hypocalcemia, presenting with acral and perioral paresthesias, neuromuscular excitability, tetany, or cardiac arrhythmias. Acute symptomatic hypocalcemia requires treatment with IV calcium until ionized calcium levels are equal to or greater than 1.0 mmol/L. Long-term supplementation with vitamin D or its analogues and oral calcium is the mainstay of management, with a goal of low normal albumin-corrected serum calcium, 24-hour urinary calcium below 300 mg/d, and a calcium-phosphate product below 55. PTH replacement therapy may emerge as an alternative, with a decreased risk of hypercalciuria. Parathyroid gland autografts when appropriately preserved and transplanted have a low incidence of permanent hypoparathyroidism and should be considered in surgeries where there is high likelihood of postoperative hypoparathyroidism.

Footnotes

Disclosure Statement

The authors have no conflict of interest.

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