Medical Care
FHH is mild, usually asymptomatic, and therefore does not require specific therapy. Treatment for NSHPT has been surgical but the development of new drugs has allowed for successful medical management in several cases. These therapies are considered experimental and include calcimimetics (cinacalcet) and bisphosphonates (pamidronate), which have been used as monotherapy or as combination therapy. [21, 22]
Cinacalcet, an allosteric modulator of the CASR, has not been approved in children and requires close supervision. Hypocalcemia has been the principal side effect described when used for NSHPT, and a trial was suspended because of one death in an older child which may or may not be related to the medication. [22, 23] A study by Bernardor et al reported that the off-label use of cinacalcet in children reduced PTH and calcium levels without a significant increase in adverse effects. [24] Bisphosphonates are similarly not approved in children but have been used more extensively in osteogenesis imperfecta and pediatric osteoporosis. Treatment is surgical if medical therapy fails, with total parathyroidectomy being the preferred approach to avoid recurrence. [25]
Patients with calcium levels at 12-14 mg/dL should be admitted to the hospital. If asymptomatic, saline hydration may suffice. The treatment of acute severe hypercalcemia (serum calcium level >14 mg/d, or 12-14 mg/dl but symptomatic) includes hydration with isotonic sodium chloride solution to restore extracellular fluid volume that may be depleted secondary to vomiting and to induce calciuresis. Loop diuretics (eg, furosemide) should be avoided as they may worsen dehydration. Additional forms of medical treatment that can be used to decrease bone resorption include calcitonin and bisphosphonates such as pamidronate or zoledronate. These rapid acting therapies may be followed by cinacalcet while awaiting surgery.
Surgical Care
Primary hyperparathyroidism due to a solitary adenoma is cured by resection of the adenoma. Total or subtotal parathyroidectomy with autotransplantation of a parathyroid gland is curative for multiglandular disease. As in adults, a minimally invasive approach with the use of intraoperative PTH (iPTH) measurements is the gold standard for surgical resection of solitary adenomas in children. [8, 1, 7, 26] Rapid PTH assays have been used more routinely in adults; Nussbaum first described the use of iPTH using sensitive immunoradiometric assay (IRMA) and demonstrated that a decrease of PTH levels to less than 40% of baseline values 15 minutes after parathyroidectomy confirmed cure. [27] According to the Miami criteria, cure is confirmed by a drop of ≥ 50% of the highest pre incision or pre excision PTH level when PTH is measured 10 min post complete resection. [28] The use of iPTH has significantly improved surgical outcome in cases with negative imaging studies. [8] Surgical outcome depends on the experience of the surgeon.
A study by Ramonell et al showed that outpatient parathyroidectomy for primary hyperparathyroidism can be safely performed in pediatric patients (aged 8-18 years). The only complications were permanent hypoparathyroidism in one patient and temporary hypocalcemia in another. [29]
Postoperative complications include transient hypocalcemia until parathyroids regain their sensitivity to circulating calcium. This requires treatment with calcitriol and calcium supplements until parathyroid function recovers. If hypocalcemia is mild calcium supplements may suffice. Hungry bone syndrome, a prolonged period of hypocalcemia, can occur postoperatively in those cases of primary hyperparathyroidism that demonstrated significant bone demineralization. Bones reaccumulate calcium at the expense of circulating levels and calcium supplements are needed for a longer time period. Finally, as in thyroid surgery, a risk of damage to the recurrent laryngeal nerve resulting in permanent hoarseness of the voice may be observed.
Outpatient care for postparathyroidectomy patients involves continued monitoring of serum calcium levels (if low at discharge) and observation of wound healing. Furthermore, care should include treatment of accompanying tumors, such as in multiple endocrine neoplasia type 1 (MEN I).
Post-parathyroidectomy, the patient's serum calcium level must be closely monitored to determine if any evidence of transient postoperative hypocalcemia or hungry bone syndrome is present. Monitor wound healing and observe for damage to the recurrent laryngeal nerve.
Cases of transient hypoparathyroidism post resection of an adenoma require treatment with calcium or calcium and calcitriol until calcemia has normalized, usually no longer than the first post-operative week. Calcium supplements may be required for a longer period in the presence of hungry bone syndrome.
Transfer to another facility is necessary only if current facilities cannot provide the expertise of an endocrinologist, or experienced surgeon. The surgeon's experience is an important factor in the outcome of parathyroidectomies.
Consultations
The primary care provider should consult a pediatric endocrinologist. Consultation with a surgeon may be obtained after consultation with the pediatric endocrinologist. A urologist would need to be involved in the case of renal calculi. Genetic counseling for the patient and family members should be offered if the diagnosis of a genetic multiple endocrine neoplasia syndrome is made.
Diet
No strict dietary requirements are necessary for management of primary hyperparathyroidism. Vitamin D deficiency should be corrected to differentiate primary from secondary hyperparathyroidism.
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Normal parathyroid glands as seen during a thyroidectomy. The large arrow points to the superior parathyroid. The thinner arrow points to the inferior parathyroid. The forceps points toward the recurrent laryngeal nerve. The patient's head is toward the right.
Tables
Cause |
Gene |
OMIM |
1. Neonate/Infant |
||
|
||
- Familial hypocalciuric hypercalcemia |
Heterozygous inactivating CASR mutations |
145980 |
- Neonatal severe hyperparathyroidism |
Homozygous inactivating CASR mutations |
239200 |
|
||
- Maternal hypoparathyroidism |
||
- Maternal pseudohypoparathyroidism |
||
- Maternal Vitamin D deficiency |
||
2. Child/adolescent |
||
|
||
- Sporadic adenomas |
||
- Familial |
||
* Familial hypocalciuric hypercalcemia (FHH) |
CASR |
145980 |
* Multiple Endocrine Neoplasia type 1 (MEN1) |
MEN1 |
131100 |
* Multiple Endocrine Neoplasia type 2a |
RET |
171400 |
* Multiple Endocrine Neoplasia type 4 |
CDKN1B |
|
* Familial hyperparathyroidism jaw tumor syndrome (HRPT2) |
CDC73 | 145001 |
|
||
- Autoantibodies to the CASR |
||
|
||
- Renal failure/post renal transplant |
||
- Chronic hyperphosphatemia |
||
- Vitamin D deficiency |
||
* Nutritional |
||
* Malabsorption |
||
-Vitamin D dependent rickets type 1 VDDR1 |
CYP27B1 | 264700 |
|
|
|
- Vitamin D dependent rickets type 2 VDDR2 |
Vitamin D receptor | 277440 |
|
|
|
-Other causes of hypocalcemia |
||
Poor intake Drugs |
