bluuebunny/crossref_metadata_2025 huggingface dataset:
A Challenging Case of Vitamin D Toxicity Responding to Cinacalcet
Authors: Addasi Noor , Johnson Jake , Davis Clifton , Bernstein Ilia , Puri Ritika , Neumeister Amy S , Drincic Andjela T , Kotwal Anupam
Published: May 2021

Background: Interest in the role of vitamin D in various physiological processes, the prevalence of its deficiency and importance of replacement has increased significantly over the past few decades. However, many formulations of vitamin D are not regulated and are available to the public without clear guidance on safe administration, which has contributed to the uptrend in the incidence and severity of vitamin D toxicity cases. Clinical Case A 57- year-old man with a medical history significant for amyotrophic lateral sclerosis, cervical myelopathy, and oropharyngeal dysphagia presented with weakness, constipation, polydipsia, polyuria and was found to have hypercalcemia with a total Calcium level of 15.5 mg/dL (n 8.6- 10.4), and albumin 4.2 g/dL (n 3.5–5.1). He soon developed acute hypoxic respiratory failure requiring prolonged intubation followed by tracheostomy. Evaluation of the hypercalcemia revealed an elevated 25-hydroxyvitamin D [25(OH)D] > 392 ng/mL (n 30–80), 1,25- dihydroxyvitamin D [1,25(OH)D] >600 pg/mL (n 19.9 - 79.3), PTH 8 pg/mL (n 12–88), and PTHrP 0.7 pmol/L (n< 4.2). The patient had initially stated that he was taking 5000 IU of vitamin D daily but further discussion with his wife revealed that he had been taking 2 teaspoons of a powder cholecalciferol preparation with 125 mcg (5000 IU of vitamin D) per 50 mg, which would be about 800,000 IU/day. He was treated with aggressive IV hydration, calcitonin and received 2 doses of pamidronate with an initial improvement in his Calcium level down to 10 mg/dL followed by recurrence of hypercalcemia. Work up for granulomatous disease and multiple myeloma revealed latent TB. At significantly elevated [25(OH)D] levels, toxicity is partially caused by the direct action of [25(OH)D] on the vitamin D receptor (VDR), and [25(OH)D] can also cross-react with the [1,25(OH)D] assay causing false elevation. Steroids were avoided because of his recent diagnosis of latent TB; hence he was started on Cinacalcet which was gradually increased to 60 mg twice a day with sustained Calcium normalization. Repeat labs showed improvement in [25(OH)D] to 292, and normalization of [1,25(OH)D] at 69.4. He was discharged on Cinacalcet 30 mg twice a day. Conclusion PTH-independent hypercalcemia is usually treated with hydration, anti-resorptive agents including bisphosphonates, denosumab and calcitonin, in addition to steroids in cases of increased 1 αλπηα-hydroxylase activity. Cinacalcet acts on the Calcium sensing receptor (CaSR) in parathyroid tissue, kidneys, bones and the intestine and was recently shown to improve hypercalcemia of malignancy in a report of 2 cases by Sheehan et al. Cinacalcet has helped our patient and might have a potential role for the prompt treatment of vitamin D toxicity, but more data is needed.
A Case of an Ectopic Parathyroid Adenoma With a Concomitant 99mTc-sestamibi-avid Papillary Thyroid Carcinoma
Authors: Castillo Cruz Maria Nikki , Ramos Celeste Ong
Published: May 2021

Background: The evaluation and management of parathyroid adenomas have improved over the years. Localization of parathyroid adenomas in patients with primary hyperparathyroidism was simplified with the use of 99mTc-sestamibi scintigraphy. In the advent of minimally invasive parathyroid surgery, use of radionuclide probes reduced the need for neck exploration and intraoperative frozen section leading to fewer complications, shorter operative time and hospitalization and rapid postoperative recovery. However, limitations of these techniques should be taken into consideration in certain cases.

Clinical Case: A 60 year-old female diagnosed with primary hyperparathyroidism presented with recurrent nephrolithiasis and osteoporosis. Initial laboratory evaluation showed elevated serum calcium and intact PTH (1.54 mmol/L and 146 pg/mL, respectively). 99mTc-sestamibi scintigraphy showed a sestamibi-avid focus in the inferior aspect of the right lobe suggestive of a parathyroid adenoma or hyperplasia. Pre-operative neck ultrasound showed non-specific thyroid parenchymal changes and nodules on both lobes with benign sonographic features. She underwent radionuclide-guided focused right parathyroidectomy. The identified enlarged right inferior parathyroid gland registered a highest reading of 70 cps on radionuclide probe. Post-operatively, repeat intact PTH level was still elevated (171.2 pg/mL). There was an interval non-demonstration of the sestamibi-avid focus in the inferior aspect of the right thyroid lobe with an increased sestamibi uptake in the left thyroid lobe compared to the previous parathyroid scan. Histopathologic examination showed a normocellular parathyroid gland and a multifocal papillary thyroid carcinoma. She underwent total thyroidectomy with central neck dissection and 4 parathyroid gland exploration with intraoperative parathyroid hormone assay. However, serial PTH monitoring after left inferior parathyroidectomy and after bilateral partial superior parathyroidectomy still showed elevated levels. Histopathologic examination showed mildly enlarged, normocellular parathyroid gland. The bilateral carotid sheath, retropharyngeal region and superior mediastinum were explored but no ectopic parathyroid tissues were seen. Post-operatively, calcium and PTH were still elevated (1.48 mmol/L and 200.5 pg/mL, respectively).

Conclusion: This case highlights the predicaments in the management of parathyroid adenomas, recognizing the possibility of false-positive sestamibi scans due to malignant thyroid nodules and the possibility of the two diseases occurring concurrently, albeit rare.
A Case of Pseudohypoparathyroidism Type 1b in Pregnancy
Authors: Balasubramanian Priyadarshini , Lupsa Beatrice
Published: May 2021

Introduction: Pseudohypoparathyroidism (PHP) type 1b is characterized by target organ resistance to PTH leading to hypocalcemia and hyperphosphatemia in the setting of elevated PTH due to abnormal imprinting that affects the regulatory elements of GNAS1. It poses challenges in management during pregnancy and lactation. We report the case of a patient who was diagnosed with PHP type 1b while pregnant. Case Presentation: A 30 year old woman, 16 weeks pregnant was referred for the evaluation of hypocalcemia. She had a history of traumatic fracture of her lower extremity and hypothyroidism treated with levothyroxine. She was noted to have hypocalcemia 1 year prior during routine labs. Family history was significant for hypothyroidism in her sister. On physical examination, she did not have phenotypic features of Albright hereditary osteodystrophy except for short stature. Before pregnancy her labs were significant for Ca 8.1 mg/dL(8.6–10.2), iCa 4.2 mg/dL(4.8–5.6), iPTH 289 pg/mL (14–64), creatinine 0.6 mg/dL(0.8–1.2), 25 vitamin D 22 ng/mL and 24 hr urine Ca 80 mg/24 hr (65-250mg). She was started on a combination of calcium citrate and carbonate 600 mg daily and vitamin D 1000 units daily. Labs while pregnant showed Ca 8.1 mg/dL, iCa 4.1 mg/dL, iPTH 184 pg/mL, PO4 4.9 mg/dL(2.5–3.5), 1,25 Vitamin D 53 pg/mL(18–72) and 25 Vitamin D 38 ng/mL. She had mild paresthesia and muscle cramps. Calcium supplements were increased to 1800 mg daily. While the urine Ca increased to 315 mg/24 hr, other biochemical parameters did not improve. Given her low Ca, high iPTH, high PO4, normal GFR and 25 vitamin D, PHP was suspected. Genetic testing showed loss of methylation at GNAS locus down to 5% (NL >43%) Diagnosis of PHP type 1b was made. Her Ca decreased the next months to a nadir of 7.9 mg/dL despite increased doses of calcium up to 1200 mg BID. Calcitriol 0.25 mcg BID was added. The rest of her pregnancy the serum Ca stayed between 8.1–8.6 mg/dL. She delivered a boy. At birth his Ca was 8.0 mg/ dL and PTH 81pg/mL. Genetic testing showed 41% methylation of GNAS. While breast feeding her Ca was 9.4 mg/dL, her calcitriol and calcium supplements were decreased. She continues to do well on calcium 630 mg daily and calcitriol 0.25 mcg daily with serum Ca between 8.5–8.8 mg/dL. Conclusion: The literature on PHP in pregnancy is scarce due to its rarity and the management is challenging due to altered calcium and vitamin D metabolism during pregnancy and lactation. The fetus draws calcium from maternal circulation and predisposes mother to hypocalcemia. Some patients may become normocalcemic during pregnancy due to placental secretion of 1,25 Vitamin D and PTHrp. There is also increased demand for calcium with lactation. There are genetic implications on the baby as it is inherited in an autosomal dominant mode. It is important to monitor calcium levels closely as there are multiple factors that could influence calcium metabolism in pregnancy.
A Case Report of Patient With Mysterious Hypercalcemia
Authors: Eldin Randa Sharag , Poku Caroline A , Camacho Pauline M
Published: May 2021

Background: Non-parathyroid hormone related hypercalcemia has a broad differential diagnosis. One of the key diagnosis to exclude is malignancy.

Case: A 41 yo male with paraplegia due to an accident at age 21, b/l BKA, stage 4 sacral pressure ulcer complicated by vesico-cutanous fistula status post ileal conduit and chronic osteomyelitis of the ischia, sacrum and pelvis was admitted with sepsis secondary to infected sacral pressure ulcer. He was noted to be hypercalcemic with corrected calcium of 13.4mg/dl. He had no previous history of hypercalcemia, kidney stones, head or neck radiation. Work up showed appropriately suppressed PTH with normal PTHrp, 1,25-dihydroxy vitamin D, 25-dihydroxy vitamin D, SPEP, UPEP and TSH. Drug induced hypercalcemia was ruled out. CT abdomen/pelvis was done and showed chronic osteomyelitis; destruction of the sacrum, ischia, pubic bones and femoral heads with enlarged inguinal lymph nodes. Review of records showed a NM bone scan done the year prior to admission to evaluate the chronic destruction of pelvic bones was negative for malignancy. Chest imaging was unremarkable. Patient underwent debridement and wash out of sacral and bilateral lower extremity wounds with bone biopsy. Pathology showed necrotic bone, chronic and acute inflammatory tissue. Calcium peaked at 17mg/dl prior to bisphosphonate, calcitonin and IVF becoming effective. Given the severity of hypercalcemia there was concern for malignancy despitethe negative work up thus Interventional Radiology was consulted for lymph node biopsy. Inguinal lymph node FNA was positive for metastatic squamous cell cancer prompting an exam under anesthesia which was negative for anal lesions. He underwent a cystoscopy which showed a large fungating mass involving the bulbar and membranous urethra with biopsies consistent with invasive and moderately differentiated keratinizing squamous cell carcinoma. Hypercalcemia resolved with treatment and he was discharged home to complete an antibiotic course prior to anticipated chemotherapy. Unfortunately, patient died prior to starting chemotherapy.

Conclusion: Hypercalcemia has been found to be associated with 30% of late stage malignancies and is a marker of poor prognosis. It is most commonly associated with hematological malignancies, such as multiple myeloma and leukemias as well solid tumors like breast carcinomas. In Hypercalcemia of malignancy, PTHrp is the causal agent in over 80% of cases with 20% of cases attributed to osteolytic mechanisms mediated by inflammatory cytokines. Less than 1% of hypercalcemia of malignancy is attributed to excess 1,25-dihydroxy vitamin D. High level of suspicion for malignancy should be presentwhen patients present moderate/severe non-PTH mediated hypercalcemia. Workup for malignancy should be pursued even with normal PTHrp.
A Complicated Case of Posterior Reversible Encephalopathy Syndrome (PRES) Secondary to Severe Hypercalcemia
Authors: Alqaisi Sura , Saand Aisha Rasool , Tapryal Neel , Alwakeel Mahmoud , Akbik Bassel
Published: May 2021

Background:PRES is a rare but severe condition with highly variable neurologic manifestations ranging from headaches to seizures, coma and radiologic findings of focal vasogenic edema1. It is commonly caused by hypertension, chronic renal failure, preeclampsia / eclampsia and immunosuppressants. We are reporting a rare presentation of PRES caused by severe hypercalcemia.

Clinical Case: A 29- year old female presented with frontal headaches, visual disturbance, emesis and confusion. Her medical history was relevant for hyperthyroidism treated with partial thyroidectomy (on methimazole) and complicated by iatrogenic hypoparathyroidism. The resulting hypocalcemia was managed with calcitriol and calcium supplementation. On presentation, the patient was awake but disoriented. Physical examination was remarkable for right-sided hemianopsia. Admission blood pressure (BP) was 192/127 suggestive of hypertensive emergency. Initial laboratory tests revealed severe hypercalcemia (calcium: 18.7 mg/dL, ionized: 2.1 mmol/L), acute kidney injury (creatinine of 2.5 mg/dL, (baseline = <1), elevated 1, 25-dihydoxy vitamin D: 65.1 pg/mL, PTH <1 pg/mL, and negative urine toxicology. Head CT without contrast revealed symmetric bilateral parieto-occipital parenchymal hypoattenuation and MRI confirmed the aforementioned findings to be consistent with PRES. The patient was admitted to the ICU and started on Nicardipine intravenous (IV) infusion, IV fluids and calcitonin. Other causes of severe hypercalcemia such as multiple myeloma and hypercalcemia of malignancy were ruled out. Home calcium and calcitriol supplements were discontinued due to suspicion of intoxication. After correction of serum calcium levels her encephalopathy, hypertension and AKI resolved. She was subsequently transferred to the medical floor in stable condition. Calcium supplementation was resumed when serum calcium level normalized and calcitriol was held until further follow up of calcium levels as outpatient.

Conclusion: Severe hypercalcemia is a rare cause of PRES secondary its effect on vascular smooth muscle vasoconstriction and increased vascular resistance leading to severe hypertension. Thus, it is imperative to establish a prompt diagnosis and rule out hypercalcemia in all patients presenting with PRES to prevent its devastating neurologic complications. Reference: Fugate JE, Rabinstein AA. Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions. Lancet Neurol. 2015 Sep;14(9):914–925. doi: 10.1016/S1474-4422(15)00111-8. Epub 2015 Jul 13. Erratum in: Lancet Neurol. 2015 Sep;14(9):874. PMID: 26184985.
An Uncommon Cause of Hypomagnesemia With Hypercalciuria and Nephrocalcinosis in a Young Woman
Authors: Rudovich Natalia N , Hahn Kai , Jonczy Malgorzata L , Wille Georg , Zerkiebel Nic
Published: May 2021

Background: Mutations of the calcium-sensing receptor (CaSR) gene resolve in a change of calcium homeostasis with autosomal dominant and/or sporadic hypocalcemia with hypercalciuria (ADH) (gain-of-function) and familial hypocalciuric hypercalcemia (loss-of-function-mutation). Additionally, genetic mutations in renal tubular transporters are also associated with hypomagnesemia, hypercalciuria and nephrocalcinosis. Such,,magnesium-losing-diseases“ are disorders like familiar hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) which shows a mutation in the Claudin 16 gene (CLD16) and the primary hypomagnesemia with secondary hypocalcaemia caused by a genetic defect in the Transient Receptor Potential Cation Channel Subfamily M Member 6 (TRPM6) gene. Clinical Case: A 35- year old woman with a first episode of pyelonephritis presented herself in our emergency unit in January 2020. Kidney ultrasound showed an advanced stage of nephrocalcinosis and normocalcemia, hypomagnesemia, suppressed PTH and hypercalciuria were observed in laboratory analyses. Several family members from her father`s side and her brother have all been diagnosed with nephrocalcinosis developed in young age. A gene sequencing of CASR and CLD16 gene provided no sequence or copy changes. Thiazide diuretic was initiated for correction of hypercalciuria, but the patient developed hypotonic blood pressure and stopped the drug. In November 2020 she unexpectedly died. Conclusions: In our patient ADH due an activating mutation of the CaSR gene was supposed, but no abnormality in gene sequence was detected. Since CaSR are not only expressed in PTH-secreting cells in the parathyroid but also along the nephron, particularly in the thick ascending limp of loop of Henle, activating mutations of CaSR gene will lead to a decreased reabsorption of divalent cations (like calcium and magnesium). Thus, this phenotype results in low or normal PTH, low or normal serum calcium levels, hypomagnesemia, high- normal urinary calcium and magnesium excretion (due to increased activation of the CaSR gene in kidneys) and nephrocalcinosis with recurrent nephrolithiasis. Thiazide diuretics are effective in these patients and vitamin D supplementation should be considered with caution. Therapeutic attempts using CASR antagonists (calcilytics) to treat ADH are currently investigated. However, familiar hypomagnesemia with hypercalciuria and nephrocalcinosis as well as primary hypomagnesemia with secondary hypocalcaemia should also be discussed as differential diagnoses in this case. The teaching point of our case is the need of magnesium testing and additional cardiological observation regarding possibly fatal arrhythmias in these subjects. Also genetic and metabolic phenotyping of all family members in such cases is important.
Bones Versus Teeth
Authors: Mammadova Aytan Siraj , Hodge MaKenzie , Folawewo Kehinde Matilda , Cobbs Elizabeth , Nunlee-Bland Gail Louise , Odonkor Wolali Akua-Sabia , Ganta Vijaya A , Zenebe Anteneh Woldetensay
Published: May 2021

Introduction: A 200% increase in population growth among those over 85 is projected in the United States by 2050. Approximately half of women over 50 will experience an osteoporotic fracture in their lifetime. Osteoporosis disproportionately affects old-old adults (those between 85 and 95) as more than half of those admitted to the hospital for hip fracture are over 80 years of age. Older adults are also likely to need dental care. The American Dental Association guidelines offer preventive recommendations for those over 60 years of age but do not address the nuances of treatment options for nonagenarian persons. This case illustrates the treatment dilemma of nonagenarians wishing to optimize both bone and dental health. Case: We have a 95-year-old performance artist, who seeks to optimize bone health in the face of recommended dental work. She has been physically active her whole life and consumes adequate quantities of calcium and Vitamin D. She doesn’t smoke but has needed periodic glucocorticoids for exacerbations of chronic lung disease. At age 84 she began ibandronate but stopped due to worsening of esophageal reflux. She was then treated with teriparatide for 2 years. DEXA scans have shown declining hip T scores from -2.8 at age 88 to -3.5 at age 94 (osteoporotic bone density: T-score lower than -2.5). Her dentist recommended the extraction of several teeth before beginning zoledronate. She refused tooth extraction and sought treatment options to enhance her bone density. Discussion: Persons of advanced age are likely to have oral health problems requiring dental treatment. Bone health treatments such as bisphosphonates and denosumab are generally safe but can potentially cause osteonecrosis of the jaw even with simple tooth extraction in old-old population. Specific guidelines are lacking for treatment to maintain bone and dental health. The American Association of Oral and Maxillofacial Surgeons suggests that extractions and implants can be conducted as usual in patients who have been treated with oral bisphosphonates for less than four years and lack other clinical risk factors. A delay of two months is suggested for those who have been treated for more than four years or has taken glucocorticoids concomitantly. The approach is uncertain for old-old adults who are taking treatment but develop a need for dental surgery. More research is needed about options for optimizing dental health while enhancing bone density in aging population.
Calciphylaxis in Association With Hungry Bone Syndrome. A Possible Risk Factor?
Authors: Arreaza Javier , Kim Ga Hee , Kim Andrew J , Dulal Jeewendra , Goulden Peter Anthony
Published: May 2021

Background:

Calciphylaxis (calcific uremic arteriolopathy) is a rare complication seen in, although not limited to, patients with end-stage renal disease (ESRD). The abnormal regulation of calcium (Ca) and phosphorus (P) homeostasis in this patient group results in intravascular Ca deposition. These patients often develop secondary/tertiary hyperparathyroidism, presenting unique treatment challenges. When patients do not respond to medical therapy, parathyroidectomy is an option that may be complicated by hungry bone syndrome (HBS). We present a case of a patient with calciphylaxis with HBS post-parathyroidectomy.

Case Report:

The patient is a 41 y.o. male with ESRD on hemodialysis who presented with lower extremity ulcers complicated by calciphylaxis. On admission, the PTH was elevated at 2200 U with a normal corrected Ca 8.7 and P 8.5. He was found to have a non-displaced pathologic fracture of the right femoral neck. CT scan of the neck revealed nodular parathyroid hyperplasia affecting all four glands. His hyperparathyroidism was managed medically with cinacalcet, phosphate binder, and sodium thiosulfate to optimize his condition before surgery.

He underwent a subtotal parathyroidectomy, with post-op course complicated by HBS. Repeat labs showed PTH 444, P 6.1, corrected Ca 7.4, and ionized Ca <4. Despite frequent repletion with IV Ca and addition of calcitriol, he remained persistently hypocalcemic with symptoms (paresthesia, perioral numbness) and prolonged QTc (560 ms) on 12-lead EKG. After weighing the more imminent risk of unstable arrhythmia versus exacerbation of HBS by targeting too high of a Ca level post-op, ICU admission was decided where Ca levels could be more closely monitored and titrated. The patient eventually demonstrated an improvement in his Ca level and symptoms.

Discussion:

This patient with ESRD complicated by hyperparathyroidism presented with ulcers and calciphylaxis refractory to medical therapy, requiring parathyroidectomy. HBS was a concern in this particular patient given his risk factors.

Hypocalcemia is an expected electrolyte imbalance that usually resolves within 2–4 days after parathyroidectomy. Severe and persistent hypocalcemia on day 4 after the procedure should raise concern for HBS. It has been shown that the risk is higher in patients who have secondary hyperparathyroidism, prolonged duration of elevated PTH, age >60, and radiologic evidence of bone disease.

ConclusionCalciphylaxis is an uncommon but potentially fatal illness seen in ESRD patients associated with Ca and P abnormalities. Whether this may increase the risk of HBS status-post parathyroidectomy is unknown; however, HBS requiring ICU management to treat refractory hypocalcemia has been reported in this group1. It is arguable that calciphylaxis may serve to identify such patients.

(1) Hassanein M, et al. BMJ Case Rep 2018;11:e226696. doi:10.1136/bcr-2018–226696
Calcitriol Induced Hyper Calcemia in Stroma Uterine Cancer Independent From PTHrp
Authors: Alam Mustafa , Lababidi Hashem , Mahad Alam , Horani Mohamad Hosam
Published: May 2021

Case Presentation: A 70-year-old female with a history of breast cancer presented with an intra-abdominal mass. The biopsy of the mass was positive for endometrial stromal sarcoma. During hospital admission, the patient was noted to have hypercalcemia attributable to her malignancy. This hypercalcemia responded positively with IV fluids with calcitonin, and the patient was discharged with oncology follow-up for chemotherapy. The patient was referred back upon repeat labs by oncology showing a calcium of 13.4 mg/dL. The physical exam at this time was unremarkable. However, labs were significant for a RDW of 16.7%, Monocyte count of 17.7 mcg/L, Creatinine of 1.24 mg/dL, Calcium of 12.8 mg/dL, and Globulin of 4.2 g/dL. Special chemistry tests came back significant for a 1,25 Dihydroxy Vitamin D level of 256.8 pg/mL, PTHrP level of 3.7 pmol/L, PTH of 18.6 pg/mL, and free kappa light chains of 47.18 mg/dL. The patient was then placed on Prednisone 20mg daily with Zometa as needed with GYN oncology follow-up.

Discussion: Paraneoplastic hypercalcemia is a relatively common finding in malignancy, affecting up to 44% of patients (Mirrakhimov, 2015). However, the etiology behind hypercalcemia ranges from increased PTHrP, osteolytic metastases, parathyroid related tumors, and uncommonly from 1,25 Hydroxy Vitamin D (Mirrakhimov, 2015). The patient presented with hypercalcemia secondary to an endometrial stromal sarcoma. The hypercalcemia was presumed to be related to PTHrP, however, serum levels of PTHrP and PTH were at the upper limits of normal, thus not sufficient to explain hypercalcemia. The elevated Vitamin D level was suspect for a calcitriol mediated hypercalcemia, a rare finding with a few case reports relating to gastrointestinal stromal tumors (Betlachin, Kim, & Oxman, 2020). The diagnosis is further backed up by the patient’s response to prednisone, which reduces 1 alpha hydroxylase activity, reducing the calcium levels. Calcitriol mediated hypercalcemia is a phenomenon that is typical of certain granulomatous diseases, but not as well defined in the literature for cancer (Kallas et al., 2010). Thus, it is important to consider calcitriol related hypercalcemia in malignancies with reduced PTH or PTHrP for proper treatment.

Mirrakhimov A. E. (2015). Hypercalcemia of Malignancy: An Update on Pathogenesis and Management. North American journal of medical sciences, 7(11), 483

Anna Betlachin, MD, Sarah Sangnim Rhee Kim, MD, Rachael Oxman, MD, MPH, Calcitriol-Mediated Hypercalcemia in a Patient With Metastatic Gastrointestinal Stromal Tumor, Journal of the Endocrine Society, Volume 4, Issue Supplement_1, April-May 2020,

Melissa Kallas, Francis Green, Martin Hewison, Christopher White, Gregory Kline, Rare Causes of Calcitriol-Mediated Hypercalcemia: A Case Report and Literature Review, The Journal of Clinical Endocrinology & Metabolism, Volume 95, Issue 7, 1 July 2010, Pages 3111.
Clinical Presentation and Management Approach in a Case of Familial Hypocalciuric Hypercalcemia Type 3 Due to APS21 Gene Mutation
Authors: Elsheikh Sahar A , Blunk Henry M , Wilhelm Scott
Published: May 2021

Familial hypocalciuric hypercalcemia (FHH) is a genetic disorder caused by dysfunctional calcium homeostasis. Thus far, three types of FHH are known to be caused by mutations inCASR (FHH1), GNA11 (FHH2), and AP2S1 (FHH3). The patient in this case report is a 36-year old male that initially presented for a second opinion after being diagnosed with Primary Hyperparathyroidism(PHPT) with subsequent parathyroidectomy done at another institute, and developed recurrent symptomatic hypercalcemia. Prior to considering this patient for further surgical options, he underwent genetic testing, which revealed he had c.43C>T (p.Arg15Cys) mutation in the AP2S1 gene diagnostic of Familial Hypocalciuric Hypercalcemia Type 3 (FHH3). The patient’s father and sister also have hypercalcemia, and have been offered genetic testing. There have been cases reported of patients with FHH3 that have symptomatic hypercalcemia and that have associated cognitive issues. Many patients with FHH can be misdiagnosed and may undergo unnecessary parathyroidectomy. This case report further elucidates the need to raise awareness of FHH.
Extreme Secretion of PTHrP From a Pancreatic Neuroendocrine Tumor, A Shift From Severe Hypercalcemia to Hypocalcemia
Authors: Nachawi Noura , Paredes Stephania , Seibert Stephen , McShane Adam , Pantalone Kevin M
Published: May 2021

Background: PTHrP-secreting pancreatic neuroendocrine tumors (PNET) are a recognized cause of malignancy associated hypercalcemia. Herein, we report a case of severe hypercalcemia due to an extreme elevation of PTHrP from a PNET, where after treatment of the hypercalcemia, symptomatic hypocalcemia occurred. Clinical Case: A 59 year-old-woman with a recurrent PNET with liver metastases undergoing an evaluation for multi-visceral transplant presented with acute confusion, nausea and vomiting. Diagnostic testing identified an extreme elevation of total calcium (Ca) [>20.1 mg/dL (8.5 - 10.2)] from two different samples [serum albumin 4.1 g/dL (3.9 - 4.9)]. The total Ca level one month earlier was 8.3 mg/dL with a serum albumin of 3.1 g/dL. Total Ca measurements were performed with the Ca Gen.2 assay on a cobas c702 chemistry analyzer (Roche Diagnostics). Results greater than the analytical measurement range (0.8 – 20.1 mg/dL) were diluted with saline and confirmed (22.6 mg/dL). A Radiometer ABL 800 Flex blood gas analyzer was used to determine the ionized Ca concentration [2.94 mmol/L (1.08 - 1.30)]. Upon presentation the serum creatinine (Cr) was 2.07 mg/dL (0.58 - 0.96); eGFR utilizing the MDRD equation 24 mL/min/1.73m2; baseline serum Cr 0.78 mg/dL. Her serum 25-OH vitamin D was 31 ng/mL (31.0 - 80.0), PTH 12 pg/mL (15 - 65), phosphate 4.3 mg/dL (2.7 - 4.8) and 1, 25-OH vitamin D 39.1 (15.0 - 60.0). PTHrP measurements were performed by ARUP Laboratories via liquid chromatography tandem mass spectrometry (LC-MS/MS) and resulted in a reported value of >2500 pmol/L (0.0 - 3.4). Her symptoms resolved and the corrected Ca gradually decreased to 8 mg/dL after treatment with IV fluids, calcitonin 200 units sc every 12 hours for 48 hours, 60 mg IV pamidronate, and five sessions of hemodialysis. Within thirteen days of receiving pamidronate, her corrected Ca slowly increased to 12mg/dL; thus, she received a single dose of 120 mg sc denosumab. Nine days later, the patient developed symptomatic hypocalcemia (7.3 mg/dL) manifested by paresthesia in the hands and feet and perioral numbness. She then received multiple doses of oral and intravenous Ca along with 50,000 units of oral ergocalciferol twice weekly. The corrected Ca normalized (8.1 mg/dL) and symptoms resolved. The patient was discharged with plans for future treatment of her underlying malignancy. Conclusion: This is the first report of a PNET producing an extreme elevation of PTHrP of higher than 2500 pmol/L, resulting in a concordant extreme elevation of total calcium within a month of documented normocalcemia. Treatment of hypercalcemia with denosumab may result in the development of hypocalcemia requiring treatment.
Hypercalcemia- A Common Abnormality With Uncommon Etiologies
Authors: Kapoor Ashutosh , Basu Ambar
Published: May 2021

Introduction: Hypercalcemia is a relatively common electrolyte abnormality which is generally associated with Parathyroid related disorders or Cancers. Rare aetiologies comprise of granulomatous disorders and haematological malignancies namely Sarcoidosis and Lymphoma. Parathyroid hormone related Peptide (PTH-rp) and Calcitriol are implicated in causing Hypercalcemia in mentioned aetiologies.

Case Details: A 57 year gentleman was admitted following a 10 day history of feeling unwell, unsteadiness in gait, constipation and mild shortness of breath (SOB) on walking uphill. His medical history comprised of Type 1 Diabetes Mellitus (DM) and Hypertension (HTN). Regular medications did not comprise of any drugs that could lead to Hypercalcemia. Biochemic he was Hypercalcemic at 3.14 (2.20–2.60). Parathyroid Hormone levels (PTH) was 0.6 (1.1–4.7 pmol/l) which excluded Parathyroid driven aetiologies. ACE levels were normal and Myeloma screen was negative. 25-OH Vitamin D levels were within Normal limits. Management: Hypercalcemia was managed with Intravenous Fluids and optimum hydration which improved his Calcium levels, followed by subsequent normalisation. Given his suppressed PTH levels, he underwent whole body imaging to assess for evidence of underlying occult malignancy. The CT imaging of his chest, abdomen and pelvis revealed widespread Lymphadenopathy and hypodense lesions in the Spleen. The report stated likely Sarcoidosis accompanied by Splenic involvement, with the main differentials being Sarcoidois versus Lymphoproliferative disorder. This was discussed with the respiratory team and Steroids were not commenced taking into account the improvement in his Calcium levels following adequate hydration and fluids. The patient has been kept under close follow up with ongoing monitoring of his clinical status.

Summary: Hypercalcemia has been described in patients with Granulomatous disorders and Haematological malignancies. The incidence of hypercalcemia in Sarcoidosis is estimated to be approximately 10%, with no association with a specific demographic. Granulomatous disorders and Haematological malignancies constitute the rare aetiologies of hypercalcemia and are characterised by a low-normal or suppressed PTH level. Diagnosis of Sarcoidosis is often challenging with the lack of gold standard tests. Serum ACE levels can be within normal limits in people with Sarcoidosis despite not being on Steroid therapy. Evaluation of serum PTH-rp and Calcitriol can aid in diagnosis and more importantly assisting in prognostication, thus guiding further management.
Intravenous Iron Induced Severe Hypophosphatemia
Authors: Guo Rong R , Sunny Sonie S , Correa Ricardo R
Published: May 2021

Introduction: Hypophosphatemia is a recently recognized adverse effect of certain intravenous iron formulations. It was previously thought to be asymptomatic and transient, however it can cause severe hypophosphatemia associated with renal phosphate wasting. We present a case of severe hypophosphatemia following intravenous ferric carboxymaltose administration.

Clinical Case: A 40-year-old female with history of iron deficiency anemia, Hashimoto’s hypothyroidism and multinodular goiter status post thyroidectomy and obesity status post gastric sleeve presents to the hospital due to dizziness, generalized weakness, bone pain and severe myalgia right after 2nd dose of 750 mg of ferric carboxymaltose administration. She received 1st dose of 750 mg of ferric carboxymaltose a week ago prior to the presentation. She was found to have severe hypophosphatemia with a phosphorus level 1.0 mg/dl (2.4 - 4.8 mg/dl), hypocalcemia with calcium level at 8.7 mg/dl, normal PTH at 40 pg/ml and normal 25-OH Vitamin D level at 59.1 ng/ml. The fractional excretion of filtered phosphate (FEPO4) was 19.5%, supporting renal phosphate wasting. She was hospitalized for 5 days and received intravenous phosphate 45 mmol on hospitalization day 1, 15 mmol on day 2 and 30 mmol on day 3. She was discharged on K-phos Neutral 250 mg TID, Calcium carbonate/Vitamin D3 600 mg/500 IU 2 tablets TID and Calcitriol 0.5 mcg daily. While she was taking K-phos Neutral, Calcitriol and Calcium carbonate/Vitamin D3, her phosphorous level was down to 1.3 mg/dl, which was 4 weeks after 1st dose of ferric carboxymatose administration. She presented to the ED and received intravenous phosphate 15 mmol. She is currently taking K-phos Neutral 250 mg QID, Calcitriol 0.5 mcg daily and Calcium carbonate/Vitamin D3 600 mg/500 IU 2 tablets TID. Her phosphorous levels ranged at 2.5 - 3.0 mg/dl. Her bone pain and myalgia have gradually improved.

Conclusion: Clinician should be aware of the side effect of hypophosphatemia following ferric carboxymaltose administration. Recent studies showed that incidence of hypophosphatemia associated with intravenous iron administration was significantly higher in ferric carboxymatose group compared with either iron isomaltoside group or ferumoxytol group. The impact of severe hypophosphatemia should be considered when choosing an intravenous iron medication.
Isolated Hepatic Sarcoidosis Presenting With Severe Hypercalcemia
Authors: Antony Mc Anto , Verma Vipin , Bello Diego , Surabhi Ritika R , Kant Ravi
Published: May 2021

Introduction:

Sarcoidosis is an inflammatory disorder of unknown etiology that can affect various organs. Lungs, intra thoracic lymph nodes and skin are the most commonly affected organs. The prevalence of hepatic sarcoidosis ranges between 5 to 30%. However, isolated hepatic sarcoidosis is rare. Hypercalcemia in sarcoidosis varies considerably due to the varying disease course and is reported to occur between 2 to 63% cases. We report a unique care of isolated liver sarcoidosis that presented with severe parathyroid hormone (PTH) independent hypercalcemia.

Case:

A 58 years old woman of Asian ethnicity with a past medical history of type 1 diabetes, hypothyroidism and chronic kidney disease presented to emergency department with headaches and altered mental status. The headaches were present since 4 weeks and was associated with polyuria and polydipsia. Non contrast CT scan of brain was negative for acute intracranial process. Physical examination revealed unremarkable vital signs and physical findings except for the altered mental status on neurological exam (orientation to self only). Initial laboratory testing revealed high corrected serum calcium 12.2 (8.0- 10.1 mg/dl), acute renal failure with high serum creatinine 2.90 (0.57–1.0 mg/dl), abnormal liver panel with elevated AST 84 (5-32U/L), ALT 85 (5–33 U/L), Alkaline Phosphatase 151 (35-104U/L). Repeat corrected serum calcium was still high at 12.4 mg/dl which prompted further evaluation to search for the etiology of hypercalcemia and testing revealed 1, 25 dihydroxy vitamin D (1, 25 vit D) mediated hypercalcemia. Labs showed low PTH 14.6 (15–65 pg/ml), normal serum protein electrophoresis, low PTH-related peptide <2.0 pmol/L, low 25 hydroxy vitamin D 20 (30–100 ng/ml) and high 1, 25 vit D 96.5 (19.9–79.3 pg/ml). Imaging evaluation revealed multiple hypodense nodules in both lobes of the liver seen on ultrasound, and CT scan of chest, abdomen and pelvis was unremarkable except for the similar liver findings. Biopsy of the liver lesion revealed non-caseating granulomas with no evidence for lymphoma and negative for acid fast bacteria and fungal organisms. Patient was treated with intravenous fluids, zoledronic acid and initiated on a course on oral prednisone that was tapered over a period of 6 months. There was a tremendous improvement in overall clinical condition. Serum calcium and 1, 25 vit D levels normalized. CT scan performed 3 months later showed complete resolution of all liver lesions.

Conclusion:

While most cases of hepatic sarcoidosis are asymptomatic and are incidentally found due to abnormal liver function tests or imaging done for other causes, we present a case of isolated hepatic sarcoidosis diagnosed due to symptomatic severe PTH independent hypercalcemia. Even though rare, extra-pulmonary sarcoidosis should be in differentials for 1, 25 vit D mediated hypercalcemia even if thoracic imaging are unremarkable.
Late-Onset Neonatal Hypocalcemia Due to Transient Hypoparathyroidism in Infant of Mother With COVID-19 at Delivery
Authors: Grundman Jody B , Persky Rebecca W , Shankar Roopa Kanakatti
Published: May 2021

Introduction: Neonatal hypocalcemia is an uncommon condition but clinical presentation can include severe manifestations such as neuromuscular irritability, tetany, seizure or cardiac conduction abnormalities that require prompt intervention to normalize calcium levels. To our knowledge there have been no reports of neonatal hypocalcemia following maternal SARS-CoV2 infection at the time of birth. Here we report a case of transient late-onset neonatal hypocalcemia complicated by maternal SARS-CoV-2 infection at the time of delivery.

Clinical Case: A 13-day old full-term appropriate for gestational age female was born to an asymptomatic mother who tested positive for SARS-CoV2 at the time of delivery. Caretakers noticed minor twitching movements in the first few days of life that were progressively worsening. Initial ionized calcium was 0.6 mmol/L, and labs at time of transfer to our hospital were notable for total calcium of 5.5mg/dL(n 8.9–9.9), and ionized calcium of 0.67mmol/L (n 1.12–1.37 mmol/L). Calcium levels improved after she received IV calcium boluses and was started on continuous IV calcium infusion. Initial phosphorus was 8.3 mg/dL (n 3.2–7.4 mg/dL) and magnesium was 1.2 mg/dL (n 1.5–2.2 mg/dL), while intact PTH was inappropriately low at 12.2 pg/mL (n 10–65 pg/mL), and urine calcium to urine creatinine ratio was below the limits of assay detection (n <0.86), consistent with a diagnosis of neonatal hypoparathyroidism. The 25-hydroxy vitamin D was 11.1 ng/mL (n 30–100 ng/mL), which may have also been a contributing factor. She had no dysmorphic features on examination concerning for 22q deletion syndrome, and tested negative for SARS-CoV2. Chromosomal microarray did not reveal clinically relevant copy number alterations or areas of homozygosity. Calcium stabilized on enteral calcium carbonate, calcitriol, and cholecalciferol, and she was weaned off of all supplementation. Prior to discharge PTH recovered to 36.9 pg/ml with a calcium of 9.9 mg/dL, phosphorus 7.7 mg/dL, normal magnesium and 25-hydroxy vitamin D (31.3 ng/ml). She was discharged on Similac PM 60/40 formula to reduce her dietary phosphorus content, and 400 IU of cholecalciferol.

Conclusions: Hypocalcemia in patients with severe COVID-19 is being increasingly reported. There is minimal data on the effect of perinatal SARS-CoV2 infections on neonatal health. While this report does not establish causation, expanding awareness of neonatal abnormalities following maternal SARS-CoV2 infection at delivery will help to recognize causal associations and improve patient care.
Mystery Case of Parathyroid Carcinoma Masquerading as a Thyroid Nodule
Authors: Jalil Fatima , Sliwinska Aleksandra , Samat Aashish G , Rosenblatt Joseph
Published: May 2021

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

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.