bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mystery Case of Parathyroid Carcinoma Masquerading as a Thyroid Nodule
Authors: Jalil Fatima , Sliwinska Aleksandra , Samat Aashish G , Rosenblatt Joseph 
Published: May 2021

Abstract
Introduction: Parathyroid carcinoma is a rare malignancy with a prevalence of 0.005%. Patients typically present with symptoms of hypercalcemia and elevated parathyroid hormone (PTH) levels. Non-functional parathyroid carcinoma presenting with neck pain and normal calcium is a unique and challenging entity. We describe a challenging case of normocalcemic parathyroid carcinoma presenting as neck pain.
Case Description: A 59-year old woman with a history of asthma, type 2 diabetes, and tobacco use presented with neck pain and swelling worsening over months. On physical exam, she was noted to have right-sided thyroid mass. CT scan of the neck showed an enlarged thyroid gland with a 1.6 cm nodule with evidence of the trachea’s compression. Subsequent thyroid US revealed a 2.1 cm dominant solid, hypoechoic nodule in the right thyroid lobe. Initial testing revealed normal calcium levels; however, PTH level was not available. FNA of the nodule was non-diagnostic with subsequent repeat FNA interpreted as benign mass. Due to suspicious imaging features and significant neck discomfort, she underwent right hemithyroidectomy. During the surgery, the nodule was noted to be invasive with evidence of extrathyroidal extension. Postoperatively calcium was 8.9 mg/dl (8.6–10.4 mg/dl), ionized calcium 4.7 mg/dl (4.8–5.6mg/dl), PTH 48 pg/mL (14–64 pg/ml), and vitamin D25OH 48 ng/dL (30-100ng/dl). TSH was mildly elevated at 4.59 uIU/ml (0.27–4.2 uIU/ml) with free T4 of 1.09 ng/dl (0.93–1.70ng/dl). The preliminary pathology report described follicular thyroid carcinoma; however, immunostains failed to confirm primary thyroid cancer. The lesion was negative for TTF-1, PAX8, TG, CEA, calcitonin, chromogranin, and synaptophysin. The tumor was strongly positive for GATA3, PTH and positive in nuclear staining for parafibroma. The specimen was evaluated by two pathologists who favored the diagnosis of parathyroid carcinoma. A separate incidental microscopic 4mm papillary thyroid carcinoma (PTC) was found and tested positive for BRAF mutation. Genetic testing for CDC73 was negative. PET scan showed increased uptake in the right thyroid bed. Given microscopic PTC and mildly elevated TSH, she was started on levothyroxine. The patient recovered successfully after the surgery with the resolution of symptoms. She was evaluated by an oncologist, and adjuvant radiation therapy was recommended.
Conclusion: Non-functional parathyroid carcinoma is a unique entity, and its diagnosis may be delayed given an atypical presentation and normal endocrine function. Differentiation between nonfunctioning parathyroid carcinoma, parathyroid adenoma, and thyroid disease based on location and proximity to the thyroid may be challenging. Although concomitant thyroid disease is not uncommon, synchronous thyroid cancer is very rare.
Night Sweats as the Presenting Symptom of Primary Hyperparathyroidism
Authors: Williams Vanessa , Jabri Hadoun , Jakoby Michael G 
Published: May 2021

Abstract
Background: Approximately 25–40% of patients report night sweats in the previous month during appointments with their primary care clinicians. The differential diagnosis for night sweats is broad, with hyperthyroidism, carcinoid syndrome, pheochromocytoma, medullary thyroid carcinoma, insulinoma, and acromegaly as established endocrine causes. We present a case of primary hyperparathyroidism (PHPT) in which the patient’s chief complaint was night sweats and resolution occurred after parathyroidectomy. Case. A 39-year-old female reported one-year of daily night sweats that required changes of clothes and bedding. She denied excessive daytime sweating, frequent palpitations, tremors, nightmares, rashes, fevers, chills, cough, headaches, dizziness, abdominal pain, diarrhea, disrupted menses, or unintentional weight loss. Vital signs and examination were unremarkable. Hypercalcemia (11.0 mg/dL, 8.6–10.3) was noted and confirmed by additional serum calcium measurements. Intact PTH ranged from 27–33 pg/mL (12–88), and 24 h urine calcium (258 mg) excluded familial hypocalciuric hypercalcemia (FHH). Parathyroid scintigraphy and neck ultrasound identified a left neck mass, and the patient underwent successful resection of a left inferior parathyroid adenoma. Hypercalcemia and night sweats initially resolved after surgery, but the patient returned six weeks later with recurrence of night sweats. Reevaluation was notable for serum calcium 10.4 mg/dL, phosphorus 2.4 mg/dL (2.5–5.0), and intact PTH 104 pg/mL. A right superior parathyroid adenoma was identified on repeat parathyroidectomy, and the patient experienced durable resolution of night sweats and hypercalcemia following her second parathyroid surgery. She was screened for multiple endocrine neoplasia type 1 (MEN1) due to multiple parathyroid tumors, though no known pathogenic menin gene variants were identified. Conclusions: A title/abstract search in PubMed linking “hyperparathyroidism” and “hypercalcemia” to “night sweats,” “sleep hyperhidrosis,” “sweating,” “hot flashes,” “hot flushes,” “diaphoresis” and “vasomotor symptoms” yielded only one relevant case of a postmenopausal woman with hot flushes unresponsive to hormone replacement that resolved after parathyroidectomy for PHPT. Hypercalcemia is known to affect central nervous system function. It is possible that in rare cases hypercalcemia alters function of the medial preoptic area, lowering the temperature threshold above which peripheral vasodilatation and perspiration occur to dissipate heat. The patient’s predisposition to only night sweats is unclear, though unlike the first patient reported with PHPT and sweating, our patient is premenopausal. This case indicates that vasomotor symptoms may occur with PHPT and resolve after successful parathyroid surgery.
Premenopausal Osteoporosis & Perfluoroalkyl Substance Exposure; Is There a Link?
Authors: Vemula Bhavana , Olajide Omolola Bolaji 
Published: May 2021

Abstract
Introduction: Perfluoroalkyl substances (PFAS) like Perflouroctanoate (PFOA) and Perflurooctane sulfonate (PFOS) are ubiquitous environmental contaminants that have been in industrial use for many years. Many known adverse effects include malignancies, reproductive and thyroid dysfunction. However, there is limited literature regarding PFAS causing low bone density. We report a case of a premenopausal woman with a history of exposure to PFAS who was recently diagnosed with osteoporosis.
Clinical Case: A 36-year-old lady with a history of hypothyroidism, on levothyroxine, presented to the orthopedics clinic with complaints of sudden onset right foot pain with no trauma. She was found to have a fracture of her right second metatarsal bone. Notably, over a period of five years she had suffered multiple fractures including metatarsal, elbow and a wrist fracture, all with minimal or no trauma. She denied smoking, alcohol, chronic steroid or PPI use, history of malabsorption, celiac disease, kidney stones, malignancy or liver problems. Her menstrual cycles were regular; she was on oral contraceptives in the past for dysmenorrhea. She is on Vitamin D supplementation and consumes adequate dairy products daily. There is no family history of hip fracture or osteoporosis. Labs showed: Calcium 8.9mg/dl, Phosphorus 2.4mg/dl (2.5–4.5mg/dl), intact PTH was 92.7pg/ml (8-97pg/ml), 24-hour urine calcium was undetectable. Vitamin D was 56.6ng/ml (30-100ng/ml). CBC, TSH, FSH, liver & kidney functions were all normal. Anti-endomysial, anti-gliadin and anti-tissue trans glutaminase antibodies were all unremarkable. IgA level was 362mg/dl (8–352 mg/dl). DXA scan revealed the lowest Z-score (-3.1) in the lumbar spine. She reported a history of exposure to PFAS with a blood level of 22.3ng/ml for PFOA and 48.4ng/ml for PFOS in the year 2005. Plan is to initiate bisphosphonate therapy for the treatment of osteoporosis.
Discussion: PFAS are known endocrine disruptive agents that have been used widely in making a wide range of consumer products including nonstick and stain-resistant coatings of cookware, food containers. Recent studies suggest that serum PFAS concentrations were associated with lower bone density. There was a higher incidence of lower lumbar spine bone density in patients exposed to PFOS. PFOA is believed to compete with calcitriol at the same binding site on Vitamin D receptor resulting in changes in the osteoblasts thereby decreasing bone mineralization.
Conclusion: There needs to be increased awareness about the association of low bone density in patients exposed to PFAS. This is especially important in the evaluation of premenopausal osteoporosis.
References: 1. Environ Health Perspect. 2016 Jan;124 (1):81–7, 2. J Clin Endocrinol Metab 2014; 99(6) 2173–2180, 3. Sci Rep 2020 Oct 8;1091):16789
Primary Hyperparathyroidism From Ectopic Parathyroid Adenoma in a Patient With Bilateral Slipped Capital Femoral Epiphysis
Authors: Vitale Rebecca J , Shieh Hester , Modi Biren P , Gordon Rebecca J 
Published: May 2021

Abstract
Background: Primary hyperparathyroidism has been reported in 13 pediatric patients presenting with slipped capital femoral epiphysis (SCFE), but never in patients with ectopic parathyroid adenoma [1]. Case report: A 12-year-old boy with obesity (BMI 99th percentile) and autism spectrum disorder presented with a limp and was found to have bilateral SCFE. Calcium was elevated to 12.3 mg/dL (reference range 8.0–10.5) with phosphorus of 3.2 mg/dL (3.0–5.7), alkaline phosphatase 775 units/L (40–360), tubular reabsorption of phosphorus 89% (&gt 95%), 25OH-vitamin D 12.1 ng/mL (30–80), 1,25OH-vitamin D 246.6 pg/mL (19.9–79.3), and PTH 1191 pg/mL (10–65). He had significant neuropsychiatric agitation but denied constipation, polyuria, and other symptoms of hypercalcemia. He had in situ pinning of the SCFE bilaterally and was hyperhydrated with minimal improvement in his calcium level. Neck ultrasound revealed no parathyroid adenoma. He was discharged on cholecalciferol 1000 IU daily with plans for outpatient Tc-99m Sestamibi scintigraphy. Following discharge, he developed significant nausea, did not tolerate the cholecalciferol, and was non-weight bearing. Repeat labs and imaging 5 days later demonstrated calcium had risen to 16.7 mg/dL with phosphorus of 2.2 mg/dL. He was admitted and calcium improved transiently to less than 12 mg/dL with intranasal calcitonin therapy. Sestamibi and subsequent CT scan revealed a 2.7x1.6x1.9 cm ectopic parathyroid adenoma in the upper anterior mediastinum. He had thoracoscopic resection of the mass, which was revealed to be intrathymic, and PTH levels fell from 1613 pg/mL pre-operatively to 76 pg/mL 30 minutes post-resection. Post-operatively, he developed hungry bone syndrome with a calcium nadir of 7.6 mg/dL and phosphorus nadir of 1.6 mg/dL, which required oral calcium and calcitriol for 10 days. With normalization of his calcium, his neuropsychiatric symptoms improved. Pathology revealed a parathyroid adenoma. Conclusion: Primary hyperparathyroidism can be associated with SCFE and should be considered even in patients with traditional risk factors for SCFE, especially with bilateral disease. Pediatric patients with primary hyperparathyroidism and negative neck imaging should be further evaluated for ectopic parathyroid adenomas. References: 1. George, G.S., Raizada, N., Jabbar, P.K., Chellamma, J., Nair, A. Slipped Capital Femoral Epiphysis in Primary Hyperparathyroidism - Case Report with Literature Review. Indian J Endocrinol Metab. 2019 Jul-Aug;23(4):491–494.
Primary Hypoparathyroidism and Chronic Kidney Disease: Is It Always Related to Treatment?
Authors: Zlatanski Todor , Simon Nicole 
Published: May 2021

Abstract
Background: Anterior neck surgery is the leading cause of acquired hypoparathyroidism. Renal failure is the most common complication of treatment for hypoparathyroidism with active vitamin D and calcium supplements. However, the contribution of hypoparathyroidism to development of CKD in the absence of treatment is not well studied.
Clinical Case: A 70-year old woman was brought to ED after she was found on the floor at home. Medical history was significant only for a partial thyroidectomy over 20 years prior, without reported post-operative complications. She was not taking any medications. Pertinent physical findings included altered mental status, hand tremors, involuntary contractions of left arm, and ashen skin. Laboratory tests upon presentation were significant for profoundly low albumin-corrected calcium of 3.68 mg/dL (n 8.6–10.2 mg/dL); low PTH 9.9 pg/dL (n 15–65 pg/dL); elevated phosphorous 8.5 mg/dL (n 2.7–4.5 mg/dL), elevated BUN 36 mg/dL (n 8–22 mg/dL), creatinine 2.76 mg/dL (n 0.5–1.3 mg/dL) and elevated CK of 4787 U/L (n 10–225 U/L). EKG showed QT interval prolongation. Head CT revealed periventricular and basal ganglia calcifications. Renal US was normal. The patient was treated with IV and PO calcium acetate and active vitamin D with resolution of the symptoms while calcium level improved. Post hospital follow-ups were significant for persistent hyperphosphatemia, which gradually improved with calcium and non-calcium phosphate binders as well as active vitamin D. Although this patient presented with acute hypocalcemia, she had chronic hypoparathyroidism as evidenced by basal ganglia calcifications. In the absence of other medical conditions, including negative PTH antibodies, or treatment for chronic hypoparathyrodism, the most likely cause of the CKD was chronic hypoparathyroidism itself.
Conclusion: Post-surgical hypoparathyroidism may develop many years after surgery and can be asymptomatic. It is essential to diagnose this condition early to avoid late complications of the disease. The kidneys are particularly affected. Conventional treatment with calcium and vitamin D analogues is associated with ectopic mineralization and can lead to CKD. Untreated hypoparathyroidism on the other hand, can also lead to CKD, posing therapeutic challenges on finding the most appropriate and balanced treatment regimen in order to prevent further renal complications. Close monitoring and optimizing therapy plays critical role in preserving renal function of patients with hypoparathyroidism.
Recurrent Atraumatic Pelvic Fractures in a Patient With Cushing’s Disease - Is DEXA Scan Really Useful to Predict the Future Fracture Risk?
Authors: Shekhda Kalyan Mansukhbhai , Rathore Ali , Ojewuyi Taofeek , Ahlquist James 
Published: May 2021

Abstract
Background: Cushing’s disease may present with a variety of clinical features, including osteoporosis and fracture. Due to the inhibitory effects of cortisol on osteoblastic activity and enhancing effects on osteoclastic activity, these patients are more prone to have osteoporotic fractures. We report a case of ACTH dependent Cushing’s disease presenting with recurrent atraumatic pelvic fractures in a woman despite normal bone mineral density for her age. Clinical Case: A 56 year-old-woman was referred to the endocrinology department for suspected Cushing’s syndrome following a recent atraumatic fracture of right pubic ramus. She had a history of weight gain and easy fatigue. On examination, she had subtle changes suggestive of Cushing’s syndrome, including mild truncal obesity, minimal bruising and moon face. She had been taking hormone replacement therapy for 3 years for the post-menopausal symptoms. Her bone mineral density was normal for her age on a recent DEXA scan [femoral neck T score: -0.9, Z score: 0.1, lumbar spine (L1-L4) T score: -1.2, Z score: -0.1]. Her vitamin D, serum calcium and parathyroid hormone levels were normal. Her 24-hour urinary cortisol was 688 nmol/day (reference range: &lt;200 nmol/day), low dose dexamethasone suppression cortisol 525 nmol/L (reference range: &lt;50 nmol/day), ACTH 96 ng/L (reference range: &lt;50 ng/L), indicating ACTH dependent Cushing syndrome. MRI pituitary showed 7 mm right sided hypoenhancing area suggestive of a pituitary microadenoma. CT neck, thorax, abdomen and pelvis did not show any source of ectopic ACTH secretion but did show generalised osteopenia, with old fractures of the ribs and left ilium. She was referred for trans-sphenoidal resection of pituitary tumour. While awaiting pituitary surgery she was treated with metyrapone: at this time she suffered a further atraumatic fracture of the left pubic ramus. Conclusion: Glucocorticoid excess predominantly affects trabecular bones (pelvis, ribs, lumbar spine) as compared to cortical bones. Due to micro-architectural changes, reduction in bone strength is disproportionately greater than would be expected from BMD measured by DEXA. Clinicians should be aware that recurrent fracture of trabecular bones may indicate Cushing’s disease even though other clinical features of cortisol excess are minimal or absent.
Severe Hypophosphatemia and Elevated FGF23 Level Following Zoledronic Acid Infusion
Authors: Betlachin Anna , Grock Shira , Ahmadi Sheila 
Published: May 2021

Abstract
Background: Severe hypophosphatemia may be seen following zoledronic acid infusion, however FGF23 elevation has not been previously reported.
Clinical Case: A 67-year-old man with Crohn’s disease status post remote ileocolonic resection, malnutrition (BMI 16.7), anemia, history of hypovitaminosis D, secondary hyperparathyroidism, and severe osteoporosis, was advised to present to the emergency room for hypocalcemia and hypophosphatemia after routine lab draw. His initial ionized calcium was 0.89 mmol/L (1.09–1.29 mmol/L) and phosphorus was 0.9 mg/dL (2.3–4.4 mg/dL), with a 25-hydroxyvitamin D level of 62 ng/mL (20–50 ng/mL), PTH of 132 pg/mL (11–51 pg/mL), and normal renal function. Hemoglobin was stable between 8–9 g/dL (13.5–17.1 g/dL). He endorsed ongoing fatigue, oral ulcers, and perioral numbness, which had been attributed to Humira infusion 2 months prior. He denied other paresthesias, carpopedal spasms, seizures, bone pain, or confusion. He reported receiving his second annual infusion of zoledronic acid 10 days prior in Turkey. He was started on high-dose oral calcium, calcitriol, and phosphate, which were continued on discharge 5 days later. Several days into his hospitalization, the patient spoke with his wife in Turkey who confirmed that his calcium and phosphorus were both within normal limits immediately prior to his infusion. A 1,25-hydroxyvitamin D level obtained during his workup was normal at 42.5 pg/mL (19.9–79.3 pg/mL), however an FGF23 level, which returned 2 weeks later, was elevated at 287 RU/mL (&lt;=180 RU/mL). Dotatate PET to rule out oncogenic osteomalacia was negative. One month later, after normalization of calcium and phosphorus levels, repeat PTH and FGF23 levels were both within normal limits.
Conclusion: This case demonstrates that a transient increase in FGF23 levels may accompany and exacerbate hypophosphatemia following zoledronic acid infusion. The mechanism for this elevation is unclear, though we speculate that in the setting of acute hypocalcemia and hypophosphatemia due to zoledronic acid infusion, secondary hyperparathyroidism may upregulate FGF23 production, which further decreases phosphorus levels. If this scenario is accurate, the transient FGF23 elevation seen is not pathologic, but physiologic. Indeed, in the patient above, calcium and phosphorus repletion lead to normalization of both PTH and FGF23.
Severe Osteomalacia and Fractures Secondary to Vitamin D Deficiency
Authors: Mathew Justin , Berger David , Tabatabaie Vafa 
Published: May 2021

Abstract
Background: Vitamin D deficiency is a common entity among the elderly. Low vitamin D levels can lead to poor bone mineralization, in addition to elevations in PTH levels with resultant increases in bone turnover. However, severe Vitamin D deficiency causing osteomalacia has become uncommon in the United States due to increased screening and treatment. Vitamin D supplementation is a mainstay of therapy for osteoporosis, yet its effect on bone density is generally thought to be modest. We present here an extreme case of vitamin D deficiency leading to severe secondary hyperparathyroidism and bone demineralization, with excellent response to supplementation.
Clinical Case: Patient was a 73-year-old woman with hypertension who presented to the ER with acute on chronic back and lower extremity pain. She had these pains for about a year, but they had worsened over the last 4 days. She had been homebound for the past 1–2 years due to severe pain while ambulating, reported a five-inch loss of height and 50 pounds weight loss, and maintained a vegan diet. She had not had medical care in 15 years. Imaging studies demonstrated a displaced left femoral neck fracture, a nondisplaced right femoral neck fracture, multilevel thoracolumbar compression fractures, and a nondisplaced right scapular fracture. Blood tests revealed normal renal function, calcium 8.6mg/dL (nl 8.5–10.5), phosphorus 2.6mg/dL (nl 2.5–4.5), and alkaline phosphatase 2,821U/L (nl 45–164). Secondary osteoporosis workup was negative for hypercalciuria or multiple myeloma, but was notable for a PTH level of 2,190 pg/mL (nl 10–65) and 25-OH Vitamin D level of &lt;5ng/mL (nl &gt;30). C-telopeptide was measured at 3,346 pg/mL (nl &lt;1000) and osteocalcin &gt;300ng/mL (nl 8–32). DEXA scan showed T-scores of -4.2 at the lumbar spine and -6.8 at the distal forearm. She was started on high-dose vitamin D supplementation, with serum Vitamin D level rising to 42.1ng/mL after 6 months of treatment. This corresponded to a decrease in PTH to 141.1pg/mL and alkaline phosphatase to 375U/L. Repeat DEXA two years later showed 52.8% increase in bone mineral density at the lumbar spine, and 27.1% increase at the forearm. The patient’s body pains have significantly improved and she is now ambulatory again.
Conclusions: Vitamin D deficiency is an uncommon cause of severe bone demineralization in the United States. However, in certain high-risk populations, it can present with debilitating osteomalacia and numerous pathologic fractures. Even in cases of osteoporosis with severe PTH elevation, Vitamin D deficiency must be ruled out as a potential secondary etiology, as it can be easily treated with potentially dramatic response.