Hypoparathyroidism (HypoPT) is a clinical condition characterized by hypocalcemia and low
parathyroid hormone levels (PTH). HypoPT is most often the result from previous neck
surgery such as thyroidectomy, parathyroidectomy and cervical dissection. It can also
result in autoimmune damage to parathyroid glands or genetic disorders. Based on analysis
of a large health plan claims database, the estimated prevalence of hypoparathyroidism in
the United States is 77,000 cases.[1] Most patients with symptoms present with
neuromuscular irritability such as muscle spam, paresthesia, laryngospasm and seizure.
Long-term complications from HypoPT include renal impairment, cataracts and basal ganglia
calcification.[2] A health-related quality of life (QoL) survey across 13 countries
showed that 84% of patients reports impacts for ability to exercise (84%), sleep (78%),
ability to work (75%) and family relationships (63%).[3] Hypoparathyroidism is typically
managed with calcium, vitamin D and at times, thiazide diuretics. Acute hypocalcemia or
severe symptomatic hypocalcemia may require intravenous calcium administration.
Recombinant Human(rh) PTH (1-84) was approved by the U.S Food and Drug Administration
(FDA) for the management of hypoparathyroidism in 2015.[4] Studies showed that rhPTH
(1-84) can reduce the need for supplemental calcium and active vitamin D and improve
patients' QoL. However, rhPTH (1-84) is only available through a registry known as Risk
Evaluation and Mitigation Strategies (REMS) due to its potential risk for development of
osteosarcoma, and patients are not frequently able to remain on this medication for the
long-term.[5] Also not every patient is responsive to rhPTH.[6] Thus, an alternative,
less costly and effective treatment is required to physiologically restore parathyroid
function.
Parathyroid gland transplant (PGTx) has been explored for the past 60 years. Groth et al.
reported the first case of parathyroid allotransplant in 1973. A 46 year-old male who
underwent subtotal parathyroidectomy due to secondary hyperparathyroidism in 1970
developed hypoparathyroidism after cadaveric renal transplantation. Four separate pieces
of homologous hyperplastic parathyroid tissue were implanted into his pectoralis muscle
52 days after renal transplantation in 1971. He was able to stop all supplementation 2
months after PGTx and his serum calcium and phosphorus had been within normal limits in
the next 12 months.[7] Since then, several successful cases of PGTx were performed on
renal transplant recipients across the world. Of all these cases, patients has already
been on immunosuppressants. [8-13] A online survey regarding patients' view about
parathyroid transplantation was conducted in the United Kingdom in 2018. Two thirds of
patient interested in further development of parathyroid transplantation. The main
concern was the possible need for immunosuppressive therapy.[14] Several case reports
attempted to use cell culture techniques [15] and microencapsulation[16] to reduce
immunogenicity to avoid immunosuppressants. However, the allograft survival rate was low
comparing to patients who take immunosuppressants.
Case Reports of PGTx in non-transplant recipients who received immunosuppressants after
transplant were reported first in Mexico in 2015 and in Germany in 2016.
Hermosillo-Sandoval et al. in Mexico reported in their case series that 5 patients with
iatrogenic hypoparathyroidism received PGTx from donors of primary hyperparathyroidism.
In the 2-year follow up, all patients reduced calcium supplement from an average of 8.4g
calcium carbonate per day to an average of 6g/day with no immunosuppression related
complications reported. Sestamibi scintigraphy and Doppler ultrasound showed 4 patients
had radiopharmaceutical uptake with blood flow. [17] Agha et al. in Germany reported a
case of a 32-year old female with iatrogenic refractory hypoparathyroidism receiving two
normal parathyroid glands from her brother. The recipient stopped PTH (1-1-84) after
transplantation and PTH levels remained within the normal range for three years after
transplantation. Neither the donor nor recipient experienced any surgical
complications.[6]
This is a non-randomized pilot study that will evaluate feasibility of parathyroid
allotransplantation using deceased donors to treat medically refractory
hypoparathyroidism in transplant-naïve patients. Patients with permanent refractory
hypoparathyroidism will be referred to parathyroid team via comprehensive transplant
institute (CTI), endocrine surgery office, faxed referral form, MD to MD personal
relationship and access center. Based upon review of referral, the parathyroid team will
decide if patient is a candidate for evaluation. If patient meets the selection criteria,
the parathyroid team will begin the telephone screening. Parathyroid team will order the
required evaluation labs (Vitamin D25 OH level, comprehensive metabolic panel (CMP),
complete blood count (CBC) with differential count, parathyroid hormone (PTH) level,
human leukocyte antigen (HLA) testing and ABO x 2). The parathyroid team will schedule
virtual consults for surgery, nutrition, pharmacy, social work, transplant financial
coordinator, and transplant education. In-person clinic visits will occur at MD
discretion. Evaluation patients will be presented by the Transplant MD and discussed by
the multidisciplinary team to determine suitability for transplant. If candidate is
suitable for transplant, proceed with listing process and expectations.
Legacy of Hope (LOH), the Organ Procurement Organization, will notify parathyroid surgeon
of any offers. Once accepted, the parathyroid surgeon will contact the kidney
Pre-Transplant Coordinator (PTC) on call regarding organ offer and crossmatch on
potential transplant candidates. If suitable for organ offer, the parathyroid team will
contact patient and begin the admission process. The endocrine procurement team will
prepare parathyroid glands for explant using standard surgical techniques. Biopsies of
each candidate parathyroid will be obtained and sent for frozen section. The Pathologist
on-call will evaluate the procured specimen to confirm the tissue as parathyroid glands.
All glands will be combined in one specimen cup in perfusion solution. The specimen will
be kept on iced saline for transport. The specimen will transported to UAB using
standardized protocols for transplant organ tissue handling.
The recipient will receive 250mg methylprednisolone intravenous in the operating room for
induction immunosuppression. The parathyroid transplantation will be performed under
local anesthesia using well established technique of implanting parathyroid tissue in the
non-dominant brachioradialis muscle. The recipient will be transferred back to the ward
after the procedure for observation.
Patients will start on postoperative immunosuppression and postoperative prophylaxis
based on UAB protocol. The patient is discharged on the same day as the procedure. In the
pre-graft function phase, the patient will receive a daily phone check-in with labs every
other day including CBC, basic metabolic panel (BMP), PTH, ionized calcium and tacrolimus
level, and clinic visits twice weekly with surgeon-performed ultrasound of graft. In the
post-graft function phase, patients will receive weekly labs for 3 months including CBC,
CMP, PTH, tacrolimus and weekly clinic visit for 3 months. Afterwards, patient will start
monthly clinic visits for 1 year. Patients will also obtain donor-specific antibody (DSA)
testing at 1, 3, 6 months after transplant and every 3 months thereafter.