Primary hyperparathyroidism

Case 1: A 19-year-old woman with a history of multiple bilateral kidney stones was hypercalcemic (11.2 mg/dL) at the time of her last admission for stones. Her parathyroid hormone was 98 pg/mL (upper limit of normal, 68). There was no family history of nephrolithiasis, hyperparathyroidism or other endocrine tumor. While it is unusual for young women to have either kidney stones or primary hyperparathyroidism this seemed an open-and-shut case. Preoperatively the surgeon had appropriate concerns because the 24-hour urine calcium excretion was only 98 mg on the first occasion and 137 mg on repeat. Additionally the sestamibi scan did not localize an adenoma. The possibility of familial hypocalciuric hypercalcemia, a condition related to inactivating mutations of the extracellular calcium-sensing receptor, was considered but specific testing did not uncover any such mutation. In general this benign condition is not associated with kidney stones, the serum calcium is not >11 mg/dL, but the PTH may be elevated. As the name would imply the urine calcium is generally low, by both the total 24-hour excretion and the fasting urine calcium/creatinine ratio. Now I am in a quandary! The patient meets more criteria for primary hyperparathyroidism requiring surgical correction than she does for familial hypocalciuric hypercalcemia for which parathyroidectomy is contraindicated.

Case 2: A 60-year-old woman has unequivocal primary hyperparathyroidism with biochemical abnormalities but no relevant clinical symptoms. She meets criteria for parathyroidectomy in that her serum calcium is 10.8 and bone density T-score is –2.9. However, she has multiple medical problems and many previous surgeries, some of which have not gone well for her. One of her surgical encounters resulted in a tracheotomy for several weeks and she has a substantial scar on her neck. She is in no hurry to undergo elective surgery. Fortunately our community is served by a number of outstanding parathyroid surgeons, none of whom would consider surgery without extensive evaluation and discussion with the patient. If preoperative localization reveals a single adenoma then the option of minimally invasive surgery, possibly under local anesthesia can be considered. Scar tissue in the soft tissues in the neck resulting from the tracheotomy may be an issue. If surgery is not accepted by the patient, what are the options? The patient is already on a bisphosphonate for her (secondary) osteoporosis, but the benefits of parathyroidectomy appear superior to bisphosphonate in this circumstance. Cinacalcet (Sensipar, Amgen) is an FDA-approved drug that activates the calcium-sensing receptor and will lower both serum calcium and PTH, although primary hyperparathyroidism is not an approved indication. This drug is mainly used in patients with secondary hyperparathyroidism associated with chronic renal failure but I have attempted to use it occasionally in patients with primary hyperparathyroidism. I use the word “attempted” advisedly because every one of those patients has discontinued that therapy because of intolerable side effects. Not really a surprise because I have only considered that approach in patients too unwell to be considered for surgical cure.

Case 3: A 47-year-old woman has recently been diagnosed with primary hyperparathyroidism on the basis of an elevated serum calcium and PTH. She is going through the menopause transition and her only symptoms are hot flashes. She has a long history of depression and is very satisfied with her current therapy for this. She has never been on lithium, a therapy known to promote parathyroid gland growth. Depression is a reported complication of primary hyperparathyroidism and, to my knowledge, all published studies of psychometric testing have demonstrated a pattern consistent with depression. More controversial is whether this can be improved by parathyroidectomy. There are a number of reports from Scandinavia supporting amelioration of symptoms following successful surgery but studies in the United States have not observed similar findings. Anecdotally there are patients who feel “better” after surgery even though they felt “well” before surgery. That does not make depression an indication for parathyroidectomy but, since the surgery is curative in more than 95% of patients with a solitary adenoma and the complication rate is extremely low when the surgery is done by an experienced endocrine surgeon, this patient has been referred to the surgeon.