Symptomatic Hypercalcemia Research Articles

Symptomatic Hypercalcemia Secondary to Hyperthyroidism

Symptomatic Hypercalcemia Secondary to Hyperthyroidism

A Rare presentation of a common Endocrine Disorder: Grave's Thyrotoxicosis induced severe symptomatic Hypercalcemia

A Rare presentation of a common Endocrine Disorder: Grave's Thyrotoxicosis induced severe symptomatic Hypercalcemia

THU472 Novel And Multifactorial Case Of Severe Hypercalcemia Due To Primary Hyperparathyroidism And Heterozygous Mutation Of CYP24A1

Abstract Disclosure: J. Liu: None. P. Angelos: None. M. Barhoum: None. R. Jain: None. Background: Mutations of CYP24A1 are known to be associated with hypercalcemia due to disruptions in 24-hydroxylase’s ability to break down 1,25-OH Vitamin D. A case involving heterozygous mutation of CYP24A1 and primary hyperparathyroidism leading to severe hypercalcemia has not been reported. Clinical Case: A 23-year-old female presented with severe fatigue and was found to be newly hypercalcemic to 13.2 mg/dL. There was no clear family history or exogenous source. Her PTH was 62 pg/mL and 1,25-OH vitamin D was elevated to 242.7 pg/mL. Her other laboratory work-up demonstrated: albumin 4.0 g/dL, magnesium 2.2 mg/dL, Phosphate 2.1 mg/dL, creatinine 0.72 mg/dL, 25OH Vitamin D 28.2ng/mL, 24hr urine calcium 150 mg/24hr, BSALP 32 ug/L, and within normal limits SPEP, PTHrP, TSH, Free T4, ACE, metanephrines, calcitonin, and ferritin. She required multiple administrations of pamidronate or zoledronic acid every 4-6 weeks. She was started on cinacalcet without substantial effect on hypercalcemia or need for bisphosphonate. She was also started on Vitamin D supplements, while further workup was pursued due to concern of non-PTH mediated causes of hypercalcemia. She had a bone scan, CT scan of the whole body, thyroid ultrasound, and Sestimibi scan that were read as normal. She was referred to an academic metabolic bone disease center. Vitamin D supplements were stopped and a 25-OH Vitamin D to 24,25-OH Vitamin D ratio was found to be elevated at 25.18 (Normal <25). She was referred to an endocrine surgeon, who felt there was localization on Sestimibi and performed a parathyroidectomy with removal of a 3.5g parathyroid adenoma. Pathology showed a parafibromin deficient parathyroid neoplasm. Genetic testing was sent for CYP24A1 and CDC73. The patient’s CYP24A1 was positive for heterozygous pathogenic mutation with normal CDC73. Post-operatively, she had a low PTH level of 14 pg/mL but normal calcium level 9.6 mg/dL. 1,25-OH Vitamin D levels decreased to normal value 58 pg/mL (reference 18-72 pg/mL). She was weaned off calcium supplements and advised to be cautious with Vitamin D supplements. Genetic counseling was recommended. Conclusion: We report a case where a young woman with severe symptomatic hypercalcemia was found to have primary hyperparathyroidism that was exacerbated by an underlying heterozygous mutation in CYP24A1. Our case suggests that patients with mild PTH elevation and severe hypercalcemia should be screened with 1,25-OH Vitamin D levels and 25-OH to 24,25OH Vitamin D ratio for CYP24A1 mutations. While gentle Vitamin D supplementation is often recommended in primary hyperparathyroidism, in patients with mild PTH elevations but severe hypercalcemia, CYP24A1 mutations should be considered, and Vitamin D supplements should be avoided. Finally, our case suggests that primary hyperparathyroidism with underlying CYP24A1 mutation may be poorly responsive to cinacalcet. Presentation: Thursday, June 15, 2023

Revision of diagnostic guidelines for parathyroid adenoma based on case reports and a literature review

<b>Introduction:</b> Parathyroid adenoma is a benign tumor that affects the parathyroid glands, small organs in the neck that produce parathyroid hormone (PTH). The most common cause of adenoma is a mutation in the MEN1 gene. When a person has a parathyroid adenoma, the affected gland produces excess PTH, which can lead to high levels of calcium in the blood (hypercalcemia). Symptoms of hypercalcemia can include fatigue, weakness, bone pain, kidney stones, excessive thirst, and urination. Diagnosis of parathyroid adenoma typically involves blood tests to measure calcium and PTH levels, as well as imaging tests such as ultrasound, CT, or MRI to locate the tumor. Treatment most often involves surgical removal of the adenoma, which effectively cures the hypercalcemia in most cases. </br></br> <b>Case reports:</b> The article presents two cases of patients with parathyroid adenoma, concentrating on the symptomatology, diagnostic workup, and treatment. We searched for and verified the recommendations in the recent literature to revise the diagnostic guidelines for this pathology.

An interesting case of severe symptomatic hypercalcaemia - primary hyperparathyroidism, tertiary hyperparathyroidism or PTH carcinoma until proven otherwise?

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Severe symptomatic hypercalcaemia associated with thymic hyperplasia and mediastinal lymphadenopathy secondary to Graves' Disease

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Abstract #1401609: A Case of Vitamin D Toxicity Associated with Weight Loss During a Low Carbohydrate Diet

Vitamin D is a commonly prescribed, fat-soluble vitamin important for calcium homeostasis and bone health. Vitamin D Toxicity (VDT) is rare and typically caused by aggressive supplementation or manufacturing errors. In epidemiologic studies, vitamin D levels correlate inversely with adiposity, and dietary weight loss is associated with increases in 25-hydroxyvitamin D [25(OH)D] level. Vitamin D is stored in adipose tissue and it is postulated that weight loss is a risk factor for the development of VDT. Here we present a case of VDT associated with weight loss during a low carbohydrate diet. A 74-year-old man with CKD stage 3a and benign prostatic hyperplasia presented to the ED with intractable emesis preceded by subacute nausea, anorexia, and constipation. He reported following a very low carbohydrate diet with intentional weight loss from 83.9kg (BMI 25.86) to 71.9kg (BMI 21.7) over five months. He reported taking Vitamin D3 250μg (10,000 IU) daily which was self-prescribed prior to admission for at least 12 months. On admission, he was mildly bradycardic and hypertensive. Laboratory evaluation in the ED revealed serum creatinine (sCr) 5.2 mg/dL (0.66-1.28, baseline 1.24 mg/dL 3 months prior), calcium 12.9 mg/dL (8.4-10.2), albumin 3.8 g/dL (3.2-4.8), and 25(OH)D >150 ng/dL (30-100). Intact PTH was suppressed at 13.2 pg/mL (14-72) and 1,25-dihydroxyvitamin D was 71 pg/mL (18-72). PTH-related protein, and serum and urine electrophoresis were within reference ranges. The patient was treated for hypercalcemia with intravenous fluids, prednisone 20mg daily, and on hospital day eight, intravenous pamidronate 30mg. Upon discharge on hospital day nine, calcium was 10.5 mg/dL. He was instructed to stop all vitamin D containing supplements. One month after discharge, sCr was 1.9 mg/dL and calcium was 8.7 mg/dL. Vitamin D is theorized to be stored in adipose tissue in clinically relevant quantities and released during weight loss. Due to the rare presentation of VDT in the setting of dietary weight loss, there are a limited number of cases described. Few clinical trials measuring serum 25(OH)D concentrations in people with obesity following weight loss have been performed. One study confirmed that patients with obesity have lower vitamin D levels that normalize after significant weight loss, supporting the hypothesis that vitamin D is stored in the adipose tissue and released following weight loss. Here we present a case of acute VDT causing symptomatic hypercalcemia after intentional dietary weight loss in the setting of chronic supratherapeutic vitamin D supplementation. As illustrated in this case, rapid weight loss in the setting of supratherapeutic doses of Vitamin D can result in VDT. Additional studies are needed to clarify the mechanisms that regulate the kinetics of vitamin D in the adipose tissue of persons with obesity.

Abstract #1406181: Complications in the Management of Hypercalcemia in a Patient with Systemic Lupus Erythematous and Lupus Nephritis During Pregnancy

Hypercalcemia can present with a multitude of symptoms including anorexia, nausea and vomiting, constipation and neuropsychiatric disturbances. There is an overlap in these symptoms with those experienced during both pregnancy and in systemic lupus erythematosus. This case report highlights the difficulties in the diagnostic evaluation and management of hypercalcemia during pregnancy. A 26-year-old female with history of Systemic lupus erythematosus (SLE) complicated by Class V lupus nephritis and antiphospholipid syndrome presented August 2022 with symptomatic hypercalcemia at 8-weeks gestation. The patient reported fatigue, nausea and vomiting and new onset severe constipation, polydipsia and polyuria. Lab work was notable for hypercalcemia with calcium 13.2 mg/dl (corrected 13.7 mg/dl for Albumin 3.4g/dl) and parathyroid hormone (PTH) 153pg/ml. No parathyroid nodules were seen on ultrasound and 1st trimester ultrasound demonstrated a single live intra-uterine pregnancy. The patient was diagnosed with primary hyperparathyroidism and started on 0.9% normal saline intravenous fluid at 200cc/hr and Furosemide 20mg/Q6H IV to promote diuresis. Despite this, calcium could not be lowered to less than 12.4 mg/dl (13.0 mg/dl albumin corrected). The patient was discharged with instructions to drink 3-4L water per day and take Furosemide 20mg daily. On follow up at 14 weeks, Calcium was still elevated at 11.9 mg/dl and reported intermittent vomiting and constipation. ENT was consulted to consider parathyroidectomy however opted for conservative management of hypercalcemia prior to delivery due to inability to localize an adenoma and exclude ectopic parathyroid on imaging. The patient was followed closely for the remainder of her pregnancy with improvement in her symptoms, however continued to have persistent hypercalcemia posing risk of materno-fetal complications. Treatment for hypercalcemia is based upon the severity and symptoms, but it is important to consider gestational age. Exceeding the upper normal limit of calcium during pregnancy of 9.5 mg/dL increases the risk of fetal complications including spontaneous abortion, still birth and neonatal tetany. There is added difficulty in determining true symptomatic hypercalcemia given the overlap in symptomatology with pregnancy. In pregnant patients undergoing parathyroid surgery, localization can be done with ultrasound rather than Sestamibi but risks missing ectopic parathyroid glands. If surgery is not recommended, there are limited therapeutic options during pregnancy for hypercalcemia. Notably, IV fluids and diuretics provide modest temporary benefit. Total serum calcium is reported to decline across gestation, likely due to plasma volume expansion, and this may temporize the harmful effects of hypercalcemia to defer surgery until after birth. There is inadequate data on the safe use of Cinacalcet during pregnancy with no known risk of teratogenicity reported in case reports. There is however an increased risk of neonatal hypocalcemia due to gestational suppression of the fetal parathyroid glands.

Abstract #1408170: Familial Hypocalciuric Hypercalcemia, Primary Hyperparathyroidism, or Both?

Primary hyperparathyroidism (PHPT) is the leading cause of hypercalcemia, and it is characterized by hypercalcemia and normal or inappropriately high levels of parathyroid hormone (PTH). Familial Hypocalciuric hypercalcemia (FHH) is a rare autosomal dominant benign disease caused by inactivating genetic mutations in the calcium sensing receptor. Genetic analyses are expensive and not widely available, making the differential diagnosis challenging. A 77-year-old male with a past medical history of hypertension and chronic kidney disease was referred to the endocrinology clinic for evaluation of hypercalcemia. Routine tests showed total corrected calcium level of 10.5 mg/dL, hypophosphatemia 2.6 mg/dL and low 24h urinary calcium of 79 mg/24h with calcium creatinine clearance ratio (CCCR) of 0.008. 25 hydroxyvitamin D, 1,25 Dihydroxyvitamin D and magnesium were normal. PTH level was 33 pg/dL (normal 15-65 pg/dL). Patient had no hypercalcemic symptoms, history of nephrolithiasis, or bone fractures. No family history of hypercalcemia. Cancer screening and PTH related peptide were normal. He was not taking hydrochlorothiazide or lithium. Renal ultrasound showed no nephrolithiasis and DXA revealed no osteoporosis. Thyroid ultrasound showed a right 1.2cm thyroid nodule without visualization of parathyroid glands. Fine-needle aspiration biopsy (FNA) of the nodule with PTH washout was benign with PTH<10. The patient was diagnosed with FHH and was monitored semiannually. Four years after the initial evaluation, total corrected calcium level was elevated at 14 mg/dL with PTH of 378 despite 25 hydroxyvitamin D level >40, repeated urinary calcium 90 mg/24h, and CCCR 0.01. His renal function was unchanged. Parathyroid scintigraphy revealed increased uptake in the right upper thyroid lobe, and thyroid ultrasound revealed increased right thyroid nodule volume. Repeat FNA was benign, this time with a PTH washout >200. The patient opted against surgical consultation for parathyroidectomy. He was treated with cinacalcet 30 mg twice daily. The co-existence of FHH and PHPT is rare. The few reported cases include patients who maintained hypercalcemia after surgical treatment of PHPT. The best cost-effective test available is a CCCR < 0.02. Our patient had CCCR measured at different times with values < 0.01 and a PTH level that over time increased by 900%. The overlap of biochemical values in patients with FHH and PHPT contributes to the challenges in the differential diagnosis and highlights the importance of close follow up with a high degree of clinical suspicion.

Hypercalcemia–leukocytosis syndrome from non-schistosomiasis-associated squamous cell carcinoma of the urinary bladder: a case report and review of the literature

BackgroundNon-schistosomiasis-associated squamous cell carcinoma of the urinary bladder is less common in the Western world. Limited information on its possible paraneoplastic syndromes exists. Leukocytosis tends to commonly be regarded by clinicians as an indication of sepsis, rather than a feature of paraneoplasia, potential surrogate marker for recurrence, and prognostic marker. Accompanying hypercalcemia may be missed entirely.Case presentationA 66-year-old Caucasian man presented with visible painless hematuria and symptomatic hypercalcemia. Investigations revealed a squamous cell carcinoma of the urinary bladder with marked leukocytosis. Hypercalcemia and leukocytosis resolved following radical cystectomy, recurred with nodal recurrence and regressed with radiotherapeutic control. Subsequently, serum leukocyte and calcium assays were included in his follow-up protocol. His survival was 20 months by the time of the report.ConclusionThis report highlights hypercalcemia–leukocytosis syndrome as a paraneoplastic manifestation of non-schistosomiasis-associated squamous cell carcinoma to reemphasize the need for clinicians to assay for calcium in the presence of leukocytosis in such patients. Prompt identification and control of the paraneoplastic derangements, with treatment of the cancer recurrence it may connote, is advocated to provide a chance for better long-term outcomes in these patients.

Mitigating the Denosumab-Induced Rebound Phenomenon with Alternating Short- and Long-Acting Anti-resorptive Therapy in a Young Boy with Severe OI Type VI.

Osteogenesis imperfecta (OI) type VI, a recessively inherited form of OI caused by mutations in SERPINF1, is a severe form distinguished by osteomalacia on bone histomorphometry. We describe a boy with severe OI type VI who was initially treated with intravenous (IV) zoledronic acid (ZA) at 1.4years of age; however, a year later he transitioned to denosumab 1mg/kg sub-cutaneously every three months in an effort to decrease fracture rates. After two years on denosumab, he presented with symptomatic hypercalcemia due to the denosumab-induced, hyper-resorptive rebound phenomenon. Laboratory parameters at the time of the rebound were as follows: elevated serum ionized calcium (1.62mmol/L, N 1.16-1.36), elevated serum creatinine due to hypercalcemia-induced muscle catabolism (83µmol/L, N 9-55), and suppressed parathyroid hormone (PTH) (< 0.7pmol/L, N 1.3-5.8). The hypercalcemia was responsive to low-dose IV pamidronate, with a rapid decline in serum ionized calcium, and otherwise normalization of the aforementioned parameters within 10days. To benefit from the powerful, albeit short-term, anti-resorptive effect of denosumab without further rebound episodes, he was treated thereafter with denosumab 1mg/kg alternating every three months with IV ZA 0.025mg/kg. Five years later, he remained on dual alternating anti-resorptive therapy without further rebound episodes, and an overall improvement in his clinical status. This novel pharmacological approach of alternating short- and long-term anti-resorptive therapy every three months has not previously been described. Our report suggests this strategy may be an effective method for prevention of the rebound phenomenon in select children for whom denosumab may be beneficial.

Parathyroid Cancer—A Rare Finding during Parathyroidectomy in High Volume Surgery Centre

Background and Objectives: Parathyroid cancer is a very rare endocrine tumor, especially in patients with secondary hyperparathyroidism due to end stage renal disease failure. This pathology is difficult to diagnose preoperatively because it has nonspecific clinical manifestations and paraclinical aspects. Our study of the literature identified 34 reported cases of parathyroid carcinoma over the last 40 years in patients undergoing dialysis. We present our experience as illustrative of the features of clinical presentation and histopathological findings of parathyroid carcinoma and assess its management considering the recent relevant literature. Materials and Methods: From January 2012 to November 2022, 650 patients with secondary hyperparathyroidism undergoing dialysis were treated at our academic Department of General Surgery and only two cases of parathyroid carcinoma were diagnosed on histopathological examination. Results: All patients presented with symptomatic hypercalcemia, with no clinical or imaging suspicion of malignant disease and were surgically treated by total parathyroidectomy. Histopathological examination revealed morphologic aspects of parathyroid carcinoma in two cases and immunostaining of Ki-67 was performed for diagnostic confirmation. Postoperative follow-up showed no signs of recurrence and no oncological adjuvant treatment or surgical reinterventions were needed. Conclusions: Parathyroid neoplasia is a particularly rare disease, that remains a challenge when it comes to diagnosis and proper management. Surgical approach is the only valid treatment to remove the malignant tissue and thus improve the patient's prognosis. Medical and oncologic treatment may be beneficial to control hypercalcemia in case of tumor recurrence.

Surgical Management and Denosumab for Aneurysmal Bone Cysts of the Spine in an Australian Tertiary Paediatric Centre.

Aneurysmal bone cysts (ABC) are rare osteolytic, benign but often locally aggressive tumours of the long bones or vertebrae. For spinal ABC, surgical management, embolisation or sclerotherapy alone often carry high morbidity and/or high recurrence rates. Interruption of receptor activator of nuclear factor-kappa B ligand (RANKL) signalling holds promise as an effective therapeutic strategy for these tumours. We aimed to review the approach to surgical management and evaluate the efficacy and safety of denosumab for ABC of the spine in children. Retrospective review of 7 patients treated with denosumab using a standardised protocol for ABC of the spine in a tertiary paediatric centre. Surgical intervention was only conducted if there was spinal instability or significant neurological impairment. Denosumab 70mg/m2 was given 4-weekly for at least 6months, followed by 2 doses of zoledronate 0.025mg/kg, aiming to prevent rebound hypercalcaemia. All patients achieved stability of the spine and resolution of neurological impairment, if present. Six patients achieved metabolic remission and have ceased denosumab without recurrence to date; the other showed clinical and radiological improvement without complete metabolic remission. Three patients developed symptomatic hypercalcaemia 5-7months after cessation of denosumab, requiring additional bisphosphonate treatment. We present our algorithm for the surgical and medical management of paediatric spinal ABC. Denosumab produced a radiological and metabolic response in all patients, with complete remission in most. Follow-up time was not long enough to evaluate the endurance of response after cessation in some patients. Incidence of rebound hypercalcaemia in this paediatric cohort was high, prompting a change to our protocol.

Scintigraphy Negative Ultrasound positive parathyroid adenoma in familial hypocalciuric hypercalcemia

Familial hypocalciuric hypercalcemia (FHH) is a rare, lifelong, benign condition with an autosomal dominant pattern of inheritance. FHH is clinically distinguished by mild to moderate PTH-dependent hypercalcemia and normal to significantly reduced urinary calcium excretion despite elevated serum calcium. FHH is usually caused by a heterozygous loss-of-function mutation in the calcium-sensing receptor gene (CASR). It should be differentiated from primary hyperparathyroidism (PHPT). The reported case of a 10-year-old girl presented with symptomatic hypercalcemia, elevated intact parathyroid hormone, and a vitamin D deficiency. 99mTc-Sestamibi scan failed to detect any abnormalities, but high-resolution ultrasound (HRUS) of the neck revealed a right inferior parathyroid adenoma, which was excised with a focused parathyroidectomy. Although the patient’s calcium and iPTH levels normalized initially, they started rising within a few days. Bangladesh J. Nuclear Med. 26(1): 62-65, 2023

BIOCHEMICAL WITH NORMAL PARATHYROID HORMONE : A CASE REPORT

Normo-hormonal primary hyperparathyroidism(NPHPT) is an uncommon condition which has been increasing in last decade. This milder biochemical entity remains incompletely understood due to lack of long term health outcomes regarding management. NPHPT poses two challenges to the surgeon, rst is when to operate and second is the use of intra-operative parathyroid hormone assay to predict the success of surgery. Here we present a 53 year old lady who came with low back ache of more than 2 years duration. It is found to have elevated calcium levels and on further evaluation found to have high normal parathyroid hormone levels in two occasions. Pre operative localization studies were done by suspecting normo-hormonal hyperparathyroidism which showed concordant lesions in both ultrasound neck and Sestamibi scan. She underwent focused parathyroidectomy with intra-operative parathyroid hormone levels which dropped in to less than 30pg/ml. Postoperative calcium was within normal limits and she was symptomatically better. In patients with symptoms of hypercalcemia, elevated calcium levels and high normal intact parathyroid hormone levels should be considered as inappropriate and should lead to the suspicion of normo-hormonal hyperparathyroidism. Intra operative parathyroid hormone levels below 30pg/ml can be utilized as an indicator of successful operation in normo-hormonal hyperparathyroidism.In symptomatic hypercalcemic patients, even if the parathyroid hormones are high normal, a further investigation should be done to locate the parathyroid adenoma and surgery is the best cure

Pathological fractures in teen and middle age women with primary hyperparathyroidism

Primary hyperparathyroidism (PHPT) is a disease commonly seen in postmenopausal women. We report two cases of pathological fractures following trivial injuries in two different age groups; the middle and teen age group presented as PHPT due to parathyroid adenoma. PHPT usually presents with symptomatic hypercalcemia and target organ damage. Biochemical manifestations in both cases are similar i.e. hypercalcemia, elevated serum intact parathyroid hormone (iPTH), and mass in the parathyroid gland. Histopathological examination is consistent with parathyroid adenoma. We highlighted these two cases due to long delay before the PHPT diagnosisisconfirmedbecause of various investigations commenced in these patients to rule out other diagnoses. Bangladesh Journal of Medical Science Vol. 22 No. 01 January’23 Page : 234-238

A Curious Case of Hypervitaminosis D-related Hypercalcemia

Abstract Hypercalcemia can manifest with various symptoms and poses diagnostic challenges due to its multifactorial etiology. This case highlights a 74-year-old patient with hypercalcemia of complex origin. The patient had a history of chronic liver disease, chronic kidney disease, and a previous episode of hypercalcemia associated with excessive oral Vitamin D intake. On admission, the patient presented with disorientation and increased drowsiness. Further evaluation revealed persistently high serum calcium levels, low parathyroid hormone levels, and elevated levels of Vitamin D. Investigations identified a duodenal nodule with multiple lymph node enlargement, suggesting a malignancy as the underlying cause. Other potential factors contributing to hypercalcemia, such as a granulomatous disease, prolonged immobilization, and a deactivating mutation of the 24-hydroxylase gene (CYP24A1), were also considered. Despite interventions, including hemodialysis and denosumab administration, the patient’s condition deteriorated due to sepsis and hypotensive shock, ultimately resulting in death. This case emphasizes the importance of considering multiple etiologies in cases of hypercalcemia in the elderly and the challenges involved in managing severe symptomatic hypercalcemia. Medical professionals must employ sound clinical reasoning and comprehensive diagnostic approaches to accurately identify and address the underlying cause. Hemodialysis may be necessary in refractory cases to achieve serum calcium normalization.

Familial hypocalciuric hypercalcaemia type 1 caused by a novel heterozygous missense variant in the CaSR gene, p(His41Arg): two case reports

BackgroundFamilial hypocalciuric hypercalcaemia (FHH) is a rare, inherited disorder of extracellular calcium sensing. It is clinically characterised by mild to moderate parathyroid hormone dependent hypercalcaemia, an autosomal dominant pattern of inheritance, and a normal to reduced urinary calcium excretion in spite of high serum calcium.Case presentationWe report two cases of FHH in a family caused by a novel pathogenic missense variant in the CaSR gene, p. His41Arg. Case 1, describes a 17 year old female with no significant past medical history, admitted with acute appendicitis requiring laparoscopic appendectomy and reporting a six month history of polydipsia. Routine investigations were significant for hypercalcaemia, corrected calcium 3.19 mmol/L (2.21-2.52mmol/L), elevated parathyroid hormone of 84pg/ml (15-65pg/ml) and a low 24-hour urine calcium of 0.75mmol/24 (2.50-7.50mmol/24). She was initially managed with intravenous fluids and Zolendronic acid with temporary normalisation of calcium though ultimately required commencement of Cinacalcet 30 mg daily for persistent symptomatic hypercalcaemia. Genetic analysis was subsequently positive for the above variant. Case 2, a 50-year-old female, was referred to the endocrine outpatient clinic for the management of type 2 diabetes and reported a longstanding history of asymptomatic hypercalcaemia which had not been investigated previously. Investigation revealed hypercalcaemia; corrected calcium of 2.6 mmol/L (reference range: 2.21–2.52 mmol/L); PTH of 53.7ng/L (reference range: 15–65 ng/L) and an elevated 24-hour urine calcium of 10 mmol/24 (2.50–7.50 mmol/24hr) with positive genetic analysis and is managed conservatively. Despite sharing this novel mutation, these cases have different phenotypes and their natural history is yet to be determined. Two further relatives are currently undergoing investigation for hypercalcaemia and the family have been referred for genetic counselling.ConclusionAccurate diagnosis of FHH and differentiation from classic primary hyperparathyroidism can be challenging, however it is essential to avoid unnecessary investigations and parathyroid surgery. Genetic analysis may be helpful in establishing a diagnosis of FHH in light of the biochemical heterogeneity in this population and overlap with other causes of hypercalcaemia.

An Interesting Case of Hypercalcemia: Intrathyroidal Parathyroid Adenoma

Hyperparathyroidism is the most common cause of hypercalcemia in the general population, with most patients presenting with mild to moderate hypercalcemia on routine bloodwork. Serum parathyroid hormone levels, followed by neck imaging studies, are helpful in diagnosing and localizing parathyroid adenomas. Ectopic parathyroid adenoma causes diagnostic challenges. Here, we present the patient case of a 65-year-old man with severe and symptomatic hypercalcemia who was found to have an intrathyroidal parathyroid adenoma, confirmed only after thyroid resection. Although imaging and laboratory results were helpful in our evaluation, pathology was the key to establishing the final diagnosis.

Hypercalcemia affected in metastatic breast cancer patients without bone metastasis: report of three cases

BackgroundSince humoral hypercalcemia of malignancy (HHM) in breast cancer patients without bone metastasis is rare, the clinical features of this condition are not fully understood.Case presentationDuring the recent 12 years, 3602 patients were diagnosed with breast cancer in our institution, and only three patients developed HHM without bone metastasis. They were all recurrent breast cancer patients with visceral metastases including the lung and the liver. It took no more than 2 months since symptomatic onset to hospitalization because of hypercalcemia. The maximum serum calcium concentrations were 15.0 mg/dL or higher. All patients had symptoms related to hypercalcemia. Treatment of hypercalcemia including hydration, calcitonin, bisphosphonate, and diuretics was initially effective in the three patients. However, two of three cases were eventually fatal because of unsuccessful treatment of breast cancer.ConclusionsThe common features of HHM without bone metastasis in breast cancer patients include acute onset, severe symptomatic hypercalcemia, and presence of visceral metastasis. Treatment of hypercalcemia decreased serum calcium level in a short period, while successful treatment of breast cancer was essential for a long-term management of HHM. This report provides a consideration to help elucidate the pathophysiology and medical care of breast cancer patients with HHM without bone metastasis.