Michael Kleerekoper, MD, MACE, has joined the faculty at the University of Toledo Medical School where he is Professor in the Department of Internal Medicine and section chief of the Endocrinology Division. The author of numerous journal studies, Dr. Kleerekoper serves on the editorial boards for Endocrine Today, Endocrine Practice, Journal of Clinical Densitometry, Journal of Women's Health, Osteoporosis International and Calcified Tissue International. Dr. Kleerekoper is also a founding board member of the newly formed Academy of Women’s Health.

A panoply of parathyroid diseases

Case one: An 80-year-old woman undergoing carotid artery evaluation was found to have a thyroid nodule which was subsequently biopsied and no malignant cells were found. Routine biochemistry revealed a serum calcium of 10.3 mg/dL and a subsequent parathyroid hormone measurement was 171 pg/mL. She was in good health but when the bone mineral density study indicated very low values in the radius I referred her to the surgeon. I am not certain why the radius is the most affected skeletal site in primary hyperparathyroidism (PHPT) as it is also in hyperthyroidism, but low BMD remains an indication for parathyroidectomy in asymptomatic patients. After consultation with the surgeon the patient agreed to parathyroidectomy. A parathyroid scan did not reveal a parathyroid lesion but that does not negate the diagnosis, nor always reflect multiple gland involvement. At surgery an adenoma was identified and removed from near the lower pole of the thyroid on the right and frozen section confirmed the diagnosis. Intraoperative parathyroid after removal of the adenoma was 10 pg/mL, a strong indicator that no other abnormal parathyroid glands were present.

Case two:A 67-year-old woman was noted to have a serum calcium of 14.1 mg/dL with a corresponding parathyroid of 170 pg/mL. The calcium and parathyroid were measured in a different lab to case one and it is just a coincidence that the actual parathyroid values are identical. These values were stable over the next six months at which time a parathyroidectomy was performed. A solitary gland was removed and intraoperative parathyroid was 35 pg/mL after gland removal. The following morning she was clinically well and the serum calcium was 9.4 mg/dL. The preliminary pathology report was equivocal about the possibility of a parathyroid cancer because of heterogeneity and extensive fibrosis in the excised tissue. The post-gland removal intraoperative parathyroid of 35 pg/mL is not as encouraging as the value of 10 pg/mL in case one. The postoperative parathyroid of 35 pg/mL is not at a suppressed level but in the middle of the reference range suggesting that there may still be active parathyroid tissue in situ. The issue in this patient is that it is often very difficult to correctly identify a parathyroid carcinoma under the microscope and the only clarification of a cancer may be recurrence of profound hypercalcemia or development of metastases some years postoperatively. This is a vexing clinical problem because, as you can imagine, the patient feels much better with a calcium of 9.4 mg/dL than she did when the calcium was 14.1 mg/dL. The surgeon and I now face the dilemma of what exactly to report to the patient. A triumphant “we got it all” may be as inappropriate as a querulous “I’m not sure we got it all.” We settled for “I’m glad you are feeling better now that your calcium is normal. We’ll keep an eye on it for a while.”

Case three: A 20-year-old woman came for a routine checkup of her hypoparathyroidism, a condition she shared with her mother who accompanied her to the clinic. Her mother had been diagnosed with hypoparathyroidism in her teens and had a stormy course while her doctors worked hard to keep her calcium close to normal. The patient had a serum calcium checked regularly while growing up and had not had hypocalcemia until 15 years of age. Her therapy with calcium and calcitriol (1-25 dihydroxyvitamin D) was very effective at maintaining normocalcemia. Mother and daughter were part of a three generation family of hypoparathyroidism – the patient’s grandfather, her brother (14 years), her sister (18 years), one of her mother’s three sisters and this aunt’s two teenage children. Hypoparathyroidism can occur as an isolated endocrine deficiency syndrome or as part of an autoimmune polyglandular failure syndrome. There is an extensive literature on familial hypoparathyroidism and several genetic abnormalities have been reported. The condition can be easily distinguished from the hypocalcemia resulting from an activating mutation of the calcium sensing receptor (CaSR) because, as in my case, the urine calcium is low, while it is most often elevated in hypocalcemia as a result from a CaSR mutation.

Case four: (Just to finish this series of "non-run of the mill" calcium issues I have seen in clinic over the past few months.) This patient is a 68-year-old woman who was referred because her calcium was high at 10.8 mg/dL but her parathyroid hormone was normal at 35 pg/mL. Her parathyroid hormone was of course not “normal”. When the parathyroid glands are all working properly, serum parathyroid hormone should be suppressed as in cases of non-parathyroid hypercalcemia. She was not sure why she had been referred because she felt well and her older sister had been living quite well with “secondary” hyperparathyroidism for years. When I asked her whether she knew the cause of her sister’s secondary hyperparathyroidism she told me that her sister had a parathyroid gland removed several years ago and her calcium had remained high. The correct diagnosis in this patient and her sister is benign familial hypocalciuric hypercalcemia resulting from an inactivating mutation of the CaSR and identified by hypercalcemia with low urine calcium – 35 mg/dL 24 hours in my patient. Parathyroidectomy is not indicated in familial hypocalciuric hypercalcemia .