Diagnosis and Treatment > Medication
Msc Metabolic Bone Diseases, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
Search for other papers by Nikolaos Asonitis in
Google Scholar
PubMed
Msc Metabolic Bone Diseases, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
Search for other papers by Eva Kassi in
Google Scholar
PubMed
Search for other papers by Michalis Kokkinos in
Google Scholar
PubMed
Search for other papers by Ilias Giovanopoulos in
Google Scholar
PubMed
Search for other papers by Foteini Petychaki in
Google Scholar
PubMed
Search for other papers by Helen Gogas in
Google Scholar
PubMed
Summary
Hypercalcemia of malignancy is the most common cause of hypercalcemia in hospitalized patients. It is associated with a poor prognosis, since it reflects an advanced cancer stage. Among all cancer in females, breast cancer is the most common malignancy, and it has the highest prevalence of hypercalcemia. Approximately 70% of patients with breast cancer have bone metastases and 10% of them will have hypercalcemia as a complication at some point in the disease. Herein, we report a 69-year-old female patient with metastatic breast cancer, who developed severe hypercalcemia in the course of her disease and was diagnosed with humoral hypercalcemia of malignancy (HHM). Intense hydration along with corticoisteroids and antiresorptive medication (calcitonin, bisphosphonates and denosumab) were administered to the patient. Despite the above treatment, serum calcium levels remain elevated and calcimimetic cinacalcet was added. Upon discontinuation of cinacalcet, calcium levels were raised and returned back to the normal levels following re-initiation of the calcimimetic. Her calcium level restored to normal, and she was discharged with the following medical treatment: denosumab monthly, and cinacalcet at a titrated dose of 90 mg per day. The patient is followed as an outpatient and 11 months later, her calcium level remained within the normal range.
Learning points:
-
Hypercalcemia of malignancy is the most common cause of hypercalcemia in hospitalized patients.
-
Breast cancer has the highest prevalence of hypercalcemia.
-
The cornerstone of therapy remains the intense hydration and intravenous bisphosphonates (preferably zoledronic acid).
-
In case of persistent hypercalcemia of malignancy, the administration of calcimimetic cinacalcet could be an additional effective therapeutic option.
Search for other papers by Marina Tsoli in
Google Scholar
PubMed
Search for other papers by Anna Angelousi in
Google Scholar
PubMed
Search for other papers by Dimitra Rontogianni in
Google Scholar
PubMed
Search for other papers by Constantine Stratakis in
Google Scholar
PubMed
Search for other papers by Gregory Kaltsas in
Google Scholar
PubMed
Summary
Parathyroid carcinoma is an extremely rare endocrine malignancy that accounts for less than 1% of cases of primary hyperparathyroidism. We report a 44-year-old woman who presented with fatigue and diffuse bone pain. Laboratory findings revealed highly elevated serum calcium and parathyroid hormone (PTH) levels and a 4.5 × 3 × 2.5 cm cystic lesion in the lower pole of the right thyroid lobe that was shown histologically to be a parathyroid carcinoma. Ten years later, the patient developed brain and pulmonary metastases and recurrence of PTH-related hypercalcemia. Treatment of hypercalcemia along with localized radiotherapy and various chemotherapy regimens failed to induce a biochemical or radiological response. In conclusion, parathyroid carcinoma is a rare neoplasia that may develop metastases even after prolonged follow-up, for which there is no evidence-based treatment besides surgery. Different chemotherapeutic schemes did not prove to be of any benefit in our case highlighting the need for registering such patients to better understand tumor biology and develop specific treatment.
Learning points:
-
Metastases can develop many years after parathyroid cancer diagnosis.
-
Surgery is the only curative treatment for parathyroid carcinoma.
-
Chemotherapy and radiotherapy prove to be ineffective in parathyroid cancer treatment.
-
Patient registering is required in order to delineate underlining pathology and offer specific treatment.
Search for other papers by Reiner Jumpertz von Schwartzenberg in
Google Scholar
PubMed
Search for other papers by Ulf Elbelt in
Google Scholar
PubMed
Search for other papers by Manfred Ventz in
Google Scholar
PubMed
Search for other papers by Knut Mai in
Google Scholar
PubMed
Search for other papers by Tina Kienitz in
Google Scholar
PubMed
Search for other papers by Lukas Maurer in
Google Scholar
PubMed
Search for other papers by Thomas Rose in
Google Scholar
PubMed
Search for other papers by Jens C Rückert in
Google Scholar
PubMed
Search for other papers by Christian J Strasburger in
Google Scholar
PubMed
Search for other papers by Joachim Spranger in
Google Scholar
PubMed
Parathyroid carcinoma is a rare disease leading to severe hypercalcemia due to hyperparathyroidism. Surgery is the primary treatment option. A more progressive form of the disease is characterized by parathyrotoxicosis, and subsequent hypercalcemia is the most common cause of death. We report a case presenting with severe hypercalcemia due to parathyrotoxicosis from parathyroid carcinoma treated for the first time using the monoclonal antibody denosumab as a rescue therapy and present long-term follow-up data. The 71-year-old patient presented with severe hypercalcemia due to metastatic parathyroid carcinoma. Despite undergoing treatment with bisphosphonates, cinacalcet hydrochloride, and forced diuresis, the patient`s condition deteriorated rapidly due to resistant hypercalcemia. Surgery performed because of spinal metastasis and forced diuresis lowered calcium levels, albeit they remained in the hypercalcemic range and significantly increased when forced diuresis was stopped. Considering a palliative situation to overcome hypercalcemia, we decided to administer denosumab, a monoclonal antibody that binds to the receptor activator of nuclear factor-kappa B ligand. After a single subcutaneous administration of 60 mg denosumab, calcium levels normalized within one day. Subsequent denosumab injections led to permanent control of serum calcium for more than 2 years despite rising parathyroid hormone levels and repeated surgeries. Together with recent cases in the literature supporting our observation, we believe that denosumab is relevant for future trials and represents an effective tool to control hypercalcemia in patients with advanced stages of parathyroid cancer.
Learning points
-
Severe hypercalcemia is the most common cause of death in patients with parathyroid carcinoma.
-
The monoclonal antibody denosumab rapidly lowered severely elevated serum calcium levels due to parathyrotoxicosis.
-
Denosumab was effective in the long-term treatment of hypercalcemia despite progression of parathyroid carcinoma.
Search for other papers by K Nadarasa in
Google Scholar
PubMed
Search for other papers by M Bailey in
Google Scholar
PubMed
Search for other papers by H Chahal in
Google Scholar
PubMed
Search for other papers by O Raja in
Google Scholar
PubMed
Search for other papers by R Bhat in
Google Scholar
PubMed
Search for other papers by C Gayle in
Google Scholar
PubMed
Search for other papers by A B Grossman in
Google Scholar
PubMed
Search for other papers by M R Druce in
Google Scholar
PubMed
Summary
We present the case of a patient with metastatic parathyroid carcinoma whose hypercalcaemia was medically managed through two pregnancies. The diagnosis was made when the patient presented with chronic knee pain and radiological findings consistent with a brown tumour, at the age of 30. Her corrected calcium and parathyroid hormone (PTH) levels were significantly elevated. Following localisation studies, a right parathyroidectomy was performed with histology revealing parathyroid carcinoma, adherent to thyroid tissue. Aged 33, following biochemical recurrence of disease, the patient underwent a second operation. A subsequent CT and FDG–PET revealed bibasal pulmonary metastases. Aged 35, the patient was referred to our unit for treatment of persistent hypercalcaemia. The focus of treatment at this time was debulking metastatic disease using radiofrequency ablation. Despite advice to the contrary, the patient conceived twice while taking cinacalcet. Even though there are limited available data regarding the use of cinacalcet in pregnancy, both pregnancies continued to term with the delivery of healthy infants, using intensive medical management for persistent hypercalcaemia.
Learning points
-
Parathyroid carcinoma is a rare cause of primary hyperparathyroidism.
-
Hypercalcaemia during pregnancy can result in significant complications for both the mother and the foetus.
-
The use of high-dose cinacalcet in pregnancy has been shown, in this case, to aid in the management of resistant hypercalcaemia without teratogenicity.
