We report that TSHR mutations occur in ∼5% thyroid nodules in a large consecutive series with indeterminate cytology. TSHR mutations may be associated with an increased cancer risk when present at high allelic frequency, even when the nodule is hyperfunctioning. Benign nodules were however most strongly correlated with TSHR mutations at low allelic frequency.

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The optimal interval for follow-up imaging of patients with prolactinomas is unclear. We wish to determine the likelihood of tumor enlargement in patients with prolactinomas who have a stable or reduced prolactin (PRL) level over time, whether or not they are treated with a dopamine agonist (DA). We identified 80 patients with prolactinomas (34 men, 46 women) who had at least two paired sets of serum PRL levels and pituitary MRIs, 3 or more months apart. Patients with hyperprolactinemia due to drug or stalk effects were excluded. The median (range) age was 45 (25-77) years. Sixty-three patients (78.8%) were treated with DA. PRL levels (ng/mL) at the initial and latest sets were 114 (0.3-15,732) and 16 (0.3-1,204), respectively. In patients with identifiable tumors, the maximum tumor diameters (mm) at the initial and latest MRI studies were 12.5 (2-60) and 12.5 (2-39) respectively, with an interval of 2.9 (0.3-9.7) years. Sixty percent of patients (n = 48) had a macroadenoma. Forty-two (52.5%) patients had either disappearance of the tumor (n = 22) or reduction (n = 20) in tumor size. In the remainder, tumor size was stable in 35 but increased in 3 patients. One of these patients, observed off therapy had a concomitant rise in PRL level. The other 2 had evidence of pituitary hemorrhage with no PRL increase. Tumor growth in prolactinoma patients with a stable or decreasing PRL level, regardless of size, is a rare event. Repetitive pituitary imaging in these patients may not be warranted.

Prolactin has been proposed as a potent coactivator of platelet aggregation, possibly contributing to thromboembolic events. The objective of the study was to evaluate the relationship between prolactinoma and deep vein thrombosis (DVT), pulmonary embolism (PE), and cerebrovascular accident (CVA). Subjects were identified from a prospectively maintained pituitary database at the Cleveland Clinic. We retrospectively reviewed the charts of 544 subjects: 347 patients with prolactinomas (prolactinoma group) and 197 patients with nonfunctional pituitary adenomas (control group). Main outcome measures were DVT, PE and CVA. We found that 19 (5.5%) patients in the prolactinoma group and five (2.5%) patients in the control group had documented DVT, PE, or CVA, but this difference was not significant (p = 0.109). However, the mean initial prolactin level was higher at the time of diagnosis among prolactinoma patients than among controls (815.23 ng/ml vs. 15.90 ng/ml; p < 0.001). Among prolactinoma patients, 15 (5.5%) of 275 patients who underwent medical treatment (with cabergoline, bromocriptine, pergolide and/or other drug) and 4 (5.6%) of 72 patients who underwent transsphenoidal surgery had documented DVT, PE, or CVA, which suggests that dopaminergic therapy did not influence the risk of thromboembolic events. Hyperprolactinemia per se does not appear to predispose to a hypercoagulable state.

INTRODUCTION Teriparatide is a recombinant endogenous parathyroid hormone. It is an anabolic medication which is FDA approved for treating Osteoporosis in postmenopausal women, men with primary or hypogonadal osteoporosis and Glucocorticoid-induced osteoporosis. Transient hypercalcemia with Teriparatide is reported in 1-3% of patients, 4-6 hours after the dose administration and lasts for 24 hours. It is thought to be through the increased renal production of 1,25-dihydroxy vitamin D, increased intestinal calcium absorption and inhibition of renal calcium excretion. We report a case of persistent hypercalcemia with Teriparatide use. CASE REPORT: A 74-year-old Caucasian female presented to the hospital with mental status changes, generalized bone pain, weight loss, and poor oral intake. Her past medical history includes Rheumatoid arthritis, Sjogren syndrome, osteoporosis with compression fractures and osteoarthritis of multiple joints. Patient’s medications include Prednisone 5 mg daily, calcitonin nasal spray, vitamin D and calcium supplements. She had previously failed bisphosphonate therapy for osteoporosis. She developed new compression fracture of L4 vertebra while being treated with Denosumab. Hence Teriparatide was started 4 months prior and she received the last dose 3 days prior to the presentation On presentation, she was noted to have severe hypercalcemia with total calcium of 17.3 mg/dL, ionized calcium of 9.4 mg/dL, albumin of 3.2 g/dL and a suppressed PTH of 3ng/L. Laboratory workup including renal function, phosphorus level, 25-hydroxyvitamin D level, 1,25-dihydroxy vitamin D, Parathyroid hormone-related peptide, Thyroid stimulating hormone, serum, and urine protein electrophoresis was unremarkable. CT scan of the neck, chest, abdomen, and pelvis showed no mass lesions or lymphadenopathy. An extensive evaluation failed to identify other causes of hypercalcemia except for immobilization. She was treated as a new onset Non-PTH dependent severe Hypercalcemia case. The patient had multiple admissions with recurrent hypercalcemia since then despite discontinuation of Teriparatide. Her calcium level normalized transiently with Intravenous fluids, an Intravenous bisphosphonate, and calcitonin. However, such treatment failed to maintain normal calcium level for more than 3-4 weeks.DISCUSSION Recurrent severe hypercalcemia with Teriparatide use is rarely reported. Although immobilization can precipitate hypercalcemia, immobilization is rarely a sole etiology of severe hypercalcemia. Our case report suggests that severe recurrent hypercalcemia can be associated with teriparatide use especially in the setting of immobilization. As far as we are aware, this is the fourth reported case of persistent hypercalcemia with Teriparatide use. This case highlights the importance of monitoring calcium levels periodically when Teriparatide is used.