THE EFFECT OF RALOXIFENE ON SERUM PROLACTIN LEVEL IN PATIENTS WITH PROLACTINOMA.

Objective: To evaluate the effect of raloxifene on prolactin (PRL) levels in addition to dopamine agonist (DA) therapy in patients with prolactinoma. Methods: We conducted a retrospective chart review of 14 patients with prolactinoma on stable dose of DA for 6 months who received raloxifene 60 mg daily, as PRL could not be normalized despite being on fairly high doses of DA. Patients were informed that raloxifene is not approved by the Food and Drug Administration for prolactinoma treatment. PRL level was measured at 1 to 6 months after starting raloxifene and at 1 to 3 months following its discontinuation. Raloxifene was stopped in 8 out of 14 patients after 2 (1 to 6) months of treatment as the absolute change in PRL level was felt to be small. Results: The median age and female/male sex ratios were 50 years (range 18 to 63 years), 6/8 respectively. The baseline DA dose was 3 mg/week (0.5 to 7 mg/week) for cabergoline and 15 mg/day for bromocriptine. Ten patients had an absolute and percentage decrease in PRL of 8.3 ng/mL (1.5 to 54.2 ng/mL) and 25.9% (8 to 55%) from baseline, respectively, after 1 to 6 months on raloxifene treatment. Among 10 patients with a decrease in PRL level, 2 (20%) achieved PRL normalization. Two patients had no change in PRL and two patients had an increase in PRL level by 22.8 ng/mL and 8.8 ng/mL (47% and 23.6%), respectively. Conclusion: Raloxifene was associated with a 25.9% (8 to 55%) decrease in PRL level in 10/14 (71%) patients with prolactinoma who were on stable doses of DA including 2 patients (14%) who achieved normoprolactinemia. Abbreviations: CV = coefficient of variation; DA = dopamine agonist; FSH = follicule-stimulating hormone; LH = luteinizing hormone; PRL = prolactin; PTTG = pituitary tumor transforming gene.

An Unusual Case of Hypercalcemia Due to Graft-Versus-Host Disease.

Background/Objective: Hypercalcemia is a common disorder with a wide differential and is most commonly related to malignancy and hyperparathyroidism. Hypercalcemia is a rarely reported consequence of graft-versus-host disease (GVHD) and may be related to a granulomatous manifestation of the common stem cell transplantation procedure. Case Report: A 67-year-old woman with a history of allogenic stem cell transplantation due to myelodysplastic syndrome presented to the bone marrow transplant clinic with dysphagia, muscle aches, and rash. She was found to have an extremely increased calcium and 1,25-dihydroxyvitamin D levels, which were ultimately corrected with administration of steroids and zoledronic acid. Discussion: While uncommon, granulomatous disease can lead to hypercalcemia via the activation of 1α-hydroxylase within macrophages, which, in turn, activates 1,25-dihydroxyvitamin D leading to an increased serum calcium level. GVHD is a common, variably presenting complication of bone marrow transplantation. Granulomatous processes related to GVHD may mediate hypercalcemia in patients with both increased calcium and 1,25-dihydroxyvitamin D levels. Conclusion: This is a rare cause of calcitriol-mediated hypercalcemia associated with GVHD. There have been cases of granulomas associated with GVHD, and this could potentially lead to ectopic production of calcitriol. We deemed GVHD to be a likely cause of the patient's calcitriol-mediated hypercalcemia because we did not find another etiology that fit the clinical findings. Physician awareness of this complication and the appropriate workup will allow future researchers to properly elucidate the etiology of this rare complication.

T-cell Lymphoblastic Lymphoma Presenting as a Pituitary Mass.

Primary pituitary T-lymphoblastic lymphoma is a rare clinical entity. A 45-year-old woman presented with headache, left-eye blurry vision, diplopia, ophthalmoplegia, and ptosis. Magnetic resonance imaging of the brain showed a sellar mass most likely consistent with a pituitary macroadenoma. Laboratory evaluation disclosed secondary hypothyroidism, secondary adrenal insufficiency, and hyperprolactinemia. The mass was removed by transsphenoidal resection, and subsequent immunophenotyping revealed T-cell lymphoblastic lymphoma. Secondary workup confirmed lymphomatous confinement to the central nervous system. Following resection, the patient's headaches improved, but she experienced persistent visual deficits and palsies of cranial nerves III, IV, and VI. The chemotherapy regimen consisted of high-dose methotrexate, followed by alternating cycles of cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride (Adriamycin), dexamethasone (cyclophosphamide, mesna, vincristine sulfate, doxorubicin hydrochloride, dexamethasone), and methotrexate/cytarabine. Since receiving chemotherapy, there has been an improvement in numbness, ptosis, left orbital pressure, and headaches. This case represents only the eighth example of T-cell primary pituitary lymphoma, and the youngest patient to receive the diagnosis.

Characteristics, staging and outcomes of differentiated thyroid cancer in patients with and without Graves' disease.

Background: The incidence of thyroid cancer has increased over the last three decades with studies showing incidence of thyroid cancer is higher among patients with Graves' Disease (GD) when compared to Toxic multinodular goiter.1 We conducted a retrospective study to further investigate characteristics and outcomes in patients with thyroid cancer and GD. Methods: We retrospectively reviewed 62 patients with a diagnosis of Differentiated Thyroid Cancer (DTC). We compared age at diagnosis, type, size of tumor, radioactive iodine (RAI) use, and DTC recurrence amongst patients with GD, non-GD patients. We used Chi-square to test for independence among categorical variables at a nominal level of 0.05; comparison was based on t-test. Results: Out of 62 patients, 29 patients had GD and DTC (47%). 94% had papillary thyroid cancer. Patients with GD were diagnosed with DTC at a younger age (mean 46 years) in comparison to patients without GD (mean 53 years). There was no difference in the type of DTC. Patients with GD had significantly smaller tumor size (mean size 1.035 cm; p value = 0.002), more Stage 1 and 2 compared to patients without GD (p-value = 0.009). Both groups of patients had similar rates of recurrence on follow up and RAI use. Conclusion: We found patients with GD had smaller tumor size, early-stage DTC when compared to patients without GD and potentially favorable prognosis. More data is needed to understand whether this is due to pathogenesis like Graves antibodies promoting tumor formation or merely earlier detection of DTC in GD.

Utility Assessment of Moderate to Severe Thyroid Eye Disease Health States.

Importance: Thyroid eye disease (TED) results in varying degrees of proptosis and diplopia negatively affecting quality of life (QoL), producing possibly substantial visual changes, disfigurement, and disability. Objective: To determine the association of varying TED severities with QoL in a non-TED population by assessing health state utility scores. Design, Setting, and Participants: This qualitative study, conducted from April 20, 2020, to April 29, 2021, assessed health states for active, moderate-severe TED, and values were elicited using time trade-off methods. Six health states of varying severity were determined from 2 placebo-controlled clinical trials (171 patients with TED and clinical activity score ≥4, ±diplopia/proptosis) and refined using interviews with US patients with TED (n = 6). Each health state description was validated by interviews with additional TED patient advocates (n = 3) and physician experts (n = 3). Health state descriptions and a QOL questionnaire were piloted and administered to a general population. Visual analog scales (VASs) were also administered to detect concurrence of the findings. Main Outcomes and Measures: TED health state utility scores and whether they differ from one another were assessed using Shapiro-Wilk, Kruskal-Wallis, pairwise Wilcoxon rank sum, and paired t tests. Results: A total of 111 participants completed time trade-off interviews. The mean (SD) utility value was 0.44 (0.34). The lowest (worse) mean utility value was observed in the most severe disease state (constant diplopia/large proptosis) with 0.30 (95% CI, 0.24-0.36), followed by constant diplopia/small proptosis (0.34; 95% CI, 0.29-0.40), intermittent or inconstant diplopia/large proptosis (0.43; 95% CI, 0.36-0.49), no diplopia/large proptosis (0.46; 95% CI, 0.40-0.52), and intermittent or inconstant diplopia/small proptosis (0.52; 95% CI, 0.45-0.58). The highest (best) mean value, 0.60 (95% CI, 0.54-0.67), was observed for the least severe disease state (no diplopia/small proptosis). Conclusions and Relevance: These findings suggest that patients with active, moderate-severe TED may have substantial disutility, with increasing severity of proptosis/diplopia more likely to have detrimental associations with QoL. These health state scores may provide a baseline for determining QoL improvement in these TED health states (utility gains) treated with new therapies.

Evaluation of Thyroid Bed Nodules on Ultrasonography after Total Thyroidectomy: Risk for Loco-Regional Recurrence of Thyroid Cancer.

OBJECTIVES: We conducted a retrospective chart review of patients with differentiated thyroid cancer who underwent total thyroidectomy to examine the correlation of the persistence of thyroid bed nodules seen on ultrasonography with subsequent loco-regional recurrence. METHODS: A total of 60 patients with differentiated thyroid cancer were identified who underwent total thyroidectomy, received (131)I therapy and had thyroid bed nodules on postoperative surveillance ultrasonography. The ultrasonographic features of the thyroid bed nodules and their progression over time along with serum thyroglobulin (Tg) levels were monitored. Those patients who demonstrated no evidence of recurrence were compared to patients who had recurrence. RESULTS: Of the 60 patients, 25% had documented cancer recurrence. Sixty percent of the patients in the recurrence group had an increase in the size of bed nodules as compared to only 7% of the patients in the group without recurrence. An increase in serum Tg of more than 2-fold was seen in 80% of the patients with recurrence and in only 13% (6/45) of the patients without cancer recurrence. The odds of identifying recurrent thyroid cancer in patients with more than a 2-fold increase in serum Tg were 80.5 greater than in patients with a less than 2-fold increase in serum Tg. The odds of identifying recurrent thyroid cancer in patients with the presence of any suspicious thyroid bed nodule were 31.5 times greater than in patients without suspicious thyroid bed nodules. CONCLUSIONS: Thyroid bed nodules on surveillance ultrasound warrant fine-needle aspiration cytology if they increase in size and number, are persistent and associated with suspicious sonographic features.

Takotsubo cardiomyopathy associated with thyrotoxicosis: a case report and review of the literature.

BACKGROUND: Takotsubo or stress-induced cardiomyopathy is a form of reversible cardiomyopathy commonly associated with emotional or physical stress. Thyrotoxicosis has been identified as a rare cause of Takotsubo cardiomyopathy, with only 12 cases reported in the literature. Here, we report a case of thyroid storm presenting with Takotsubo cardiomyopathy in the setting of Graves' disease. PATIENT FINDINGS: A 71-year-old woman presented with abdominal pain, vomiting, confusion, and history of weight loss. She was initially diagnosed and treated for diabetic ketoacidosis at another hospital and was transferred to our hospital one day after initial presentation because of concern for acute coronary syndrome. A diagnosis of Takotsubo cardiomyopathy was made on the basis of cardiac catheterization. At that time, she was diagnosed and treated for thyroid storm. Follow-up 7 weeks later revealed improvement of her cardiac function and near-normalization of thyroid hormone levels. SUMMARY: In this patient, who presented with symptoms of heart failure, acute coronary syndrome was initially considered, but the diagnosis of Takotsubo cardiomyopathy associated with thyroid storm was ultimately made based on cardiac catheterization and laboratory investigation. CONCLUSIONS: Thyrotoxicosis is associated with adverse disturbances in the cardiovascular system. Takotsubo cardiomyopathy could be a presenting manifestation of thyroid storm, perhaps related to excess catecholamine levels or sensitivity.