PTH-independent Hypercalcemia Research Articles

Silicone Granulomatous Inflammation Resulting in Hypercalcemia: A Review of the Literature

Silicone usage for cosmetic enhancement is common, although it is not approved by the U.S. Food and Drug Administration. Granulomatous inflammation leading to hypercalcemia is a rare complication. We present a case of non-parathyroid hormone (PTH), calcitriol-mediated hypercalcemia in a woman with a history of cosmetic injections. Case report and review of the literature. A 48-year-old female with metabolic syndrome was evaluated for severe hypercalcemia (calcium >15 mg/dL). Laboratory tests revealed low-normal PTH, normal 25-hydroxyvitamin D, elevated 1,25-dihydroxyvitamin D, and hypercalciuria. Imaging studies, including a computed tomography (CT) scan of the lungs, was nonrevealing. Positron emission tomography/CT showed symmetric hypermetabolic subcutaneous stranding of bilateral gluteus and proximal thighs. She admitted to silicone injections in the buttocks 10 years prior. Her examination was unremarkable except for an intermittent pruritic rash over the right thigh. Labs revealed total serum calcium 11.3 mg/dL, PTH 18 pg/mL, 24-hour urinary calcium 509 mg, and PTH-related peptide 18 pg/mL. Serum and urine electrophoresis were normal, 25-hydroxyvitamin D was 47 pg/mL, and 1,25-dihydroxyvitamin D was 121 pg/mL. Angiotensin-converting enzyme level was 80 U/mL. A diagnosis of granulomatous inflammation resulting in calcitriol-mediated, PTH-independent hypercalcemia was entertained. Silicone-induced hypercalcemia should be thought of in those with prior cosmetic injections. Tissue biopsy confirms the diagnosis, which is often delayed. We reviewed 19 cases with silicone usage and variable levels of hypercalcemia. Renal injury was common. One death was reported. Glucocorticoids, calcium restriction, and hydration have been used to treat calcitriol-mediated hypercalcemia but are not curative. Ketoconazole and bisphosphonates have been used with variable success. Surgical excision tends to be ineffective due to silicone migration. The treatment of this disorder is difficult and often ineffective.

Hypercalcemic Disorders in Children.

ABSTRACTHypercalcemia is defined as a serum calcium concentration that is greater than two standard deviations above the normal mean, which in children may vary with age and sex, reflecting changes in the normal physiology at each developmental stage. Hypercalcemic disorders in children may present with hypotonia, poor feeding, vomiting, constipation, abdominal pain, lethargy, polyuria, dehydration, failure to thrive, and seizures. In severe cases renal failure, pancreatitis and reduced consciousness may also occur and older children and adolescents may present with psychiatric symptoms. The causes of hypercalcemia in children can be classified as parathyroid hormone (PTH)‐dependent or PTH‐independent, and may be congenital or acquired. PTH‐independent hypercalcemia, ie, hypercalcemia associated with a suppressed PTH, is commoner in children than PTH‐dependent hypercalcemia. Acquired causes of PTH‐independent hypercalcemia in children include hypervitaminosis; granulomatous disorders, and endocrinopathies. Congenital syndromes associated with PTH‐independent hypercalcemia include idiopathic infantile hypercalcemia (IIH), William's syndrome, and inborn errors of metabolism. PTH‐dependent hypercalcemia is usually caused by parathyroid tumors, which may give rise to primary hyperparathyroidism (PHPT) or tertiary hyperparathyroidism, which usually arises in association with chronic renal failure and in the treatment of hypophosphatemic rickets. Acquired causes of PTH‐dependent hypercalcemia in neonates include maternal hypocalcemia and extracorporeal membrane oxygenation. PHPT usually occurs as an isolated nonsyndromic and nonhereditary endocrinopathy, but may also occur as a hereditary hypercalcemic disorder such as familial hypocalciuric hypercalcemia, neonatal severe primary hyperparathyroidism, and familial isolated primary hyperparathyroidism, and less commonly, as part of inherited complex syndromic disorders such as multiple endocrine neoplasia (MEN). Advances in identifying the genetic causes have resulted in increased understanding of the underlying biological pathways and improvements in diagnosis. The management of symptomatic hypercalcemia includes interventions such as fluids, antiresorptive medications, and parathyroid surgery. This article presents a clinical, biochemical, and genetic approach to investigating the causes of pediatric hypercalcemia. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

Hypercalcaemia preceding diagnosis of Pneumocystis jirovecii pneumonia in renal transplant recipients.

BackgroundThe overall incidence of Pneumocystis jirovecii pneumonia (PJP) in solid organ transplant recipients is 5–15%. A timely diagnosis of PJP is difficult and relies on imaging and detection of the organism.MethodsWe present a case series of four patients displaying hypercalcaemia with an eventual diagnosis of PJP and document the management of the outbreak with a multidisciplinary team approach. We discuss the underlying pathophysiology and previous reports of hypercalcaemia preceding a diagnosis of PJP. We also reviewed the evidence concerning PJP diagnosis and treatment.ResultsWithin our renal transplant cohort, four patients presented within 7 months with hypercalcaemia followed by an eventual diagnosis of PJP. We measured their corrected calcium, parathyroid hormone (PTH), 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] and 25-hydroxycholecalciferol [25(OH)D] levels at admission and following treatment of PJP. All four patients diagnosed with PJP were 4–20 years post-transplantation. Three of the four patients demonstrated PTH-independent hypercalcaemia (corrected calcium >3.0 mmol/L). The presence of high 1,25(OH)2D3 and low 25(OH)D levels suggest negation of the negative feedback mechanism possibly due to an extrarenal source; in this case, the alveolar macrophages. All four patients had resolution of their hypercalcaemia after treatment of PJP.ConclusionsGiven the outbreak of PJP in our renal transplant cohort, and based on previous experience from other units nationally, we implemented cohort-wide prophylaxis with trimethoprim–sulphamethoxazole for 12 months in consultation with our local infectious diseases unit. Within this period there have been no further local cases of PJP.

PTH independent hypercalcaemia - diagnosis dilemma

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

Sudden onset of parathyroid hormone-independent severe hypercalcemia from reversal of tumoral calcinosis in a dialysis patient.

BackgroundTumoral calcinosis is a rare manifestation of extraskeletal calcification, featuring large calcified cystic masses in the periarticular regions of large joints. In chronic kidney disease (CKD), this disorder is thought to evolve through a chronically elevated calcium-phosphorus solubility product leading to calcium precipitation in soft tissue. Treating tumoral calcinosis in these patients involves interventions to lower the calcium-phosphorus product such as reduction in vitamin D therapy and intensive hemodialysis regimens.Case PresentationWe report the case of a 54-year old woman with polycystic kidney disease on peritoneal dialysis with widespread tumoral calcinosis in the context of hypercalcemic tertiary hyperparathyroidism who had been on long-term alfacalcidol therapy. After withdrawal of the vitamin D analogue and initiation of daily hemodialysis, there was rapid dissolution of her tumoral calcium deposits with the abrupt onset of parathyroid hormone (PTH)-independent transient hypercalcemia that resolved once the soft tissue deposits disappeared.ConclusionsResorption of soft tissue calcific deposits may result in transient parathyroid hormone (PTH)-independent hypercalcemia. In CKD patients, this hypercalcemia causes a decrease in the PTH level, distinguishing it from tertiary hyperparathyroidism, though PTH may not be totally suppressed, the way it is seen in PTH-independent hypercalcemia in non-CKD patients.

69-Year-Old Woman With Confusion and Fatigue

Resident in Internal Medicine, Mayo School of Graduate Medical Education, Rochester, MN (H.M.K.); Advisor to resident and Consultant in Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN (A.E.K.). A 69-year-old woman presented to her primary care physicianwith a 4-day history of fatigue and dizziness. She was 45 minutes late for her appointment because she had trouble driving to the office. She reported no motor or sensory deficits but had difficulty with coordination. Review of systems was positive for dysuria and urinary frequency. She did not have fever, chills, weight or appetite changes, respiratory, cardiac, or gastrointestinal symptoms, or recent head trauma. The patient’s medical history was remarkable for hypertension, hyperlipidemia, type 2 diabetes mellitus, osteoporosis, and gastroesophageal reflux disease. Medications included metoprolol tartrate, lisinopril with hydrochlorothiazide, lovastatin, cholecalciferol, and as-needed calcium carbonate. She had smoked half a pack of cigarettes per day for 40 years but had quit smoking 6 years previously. She didnot use alcohol or illicit drugs. On examination, the patient was afebrile with a blood pressure of 104/67 mm Hg, heart rate of 76 beats/min, respiratory rate of 17 breaths/min, oxygen saturation of 94% while breathing room air, and body mass index (calculated as weight in kilograms divided by height inmeters squared) of 39 kg/m. Shewas alert and oriented to person, place, and time. Her speech was dysarthric, and she had difficulty following simple commands. Her coordination was impaired with symmetric dysmetria on finger-to-nose testing, heel-kneeshin testing, and rapid alternating movements. Cranial nerves II through XII were intact. Results of motor and sensory examinations were within normal limits. Reflexes were symmetric. Lymph node, thyroid, cardiac, respiratory, gastrointestinal, musculoskeletal, and skin examinations identified no abnormalities.

PTH‐independent hypercalcaemia and non‐melanoma skin cancer

Recently, it became more evident that skin is a target for neuroendocrine signals. (1) To evaluate the relationship between tumour aggressiveness and hypercalcaemia in patients with non-melanoma skin cancer; (2) to identify clinical, functional, biological alterations caused by this setting; (3) calcium redistribution from extracellular fluids to intracellular compartments; (4) to describe several molecular aspects of hypercalcaemia development. This study was conducted between January 2000 and May 2009 in Dermatoveneorological Center, Bucharest. From the 1232 cases that were investigated, there were 32 patients with keratoachantoma, 468 patients with basal cell carcinoma, 412 patients with squamous cell carcinoma and 320 healthy volunteers. All the patients were screened by clinical and paraclinical examinations (haematology, biochemistry, immunology). After biochemical confirmation of hypercalcaemia, patients had endocrine tests, electrocardiography and imagistic approaches. Total serum calcium was measured in extracellular fluids (serum, urine) by spectrophotometric methods. Ionized calcium was calculated depending on total serum calcium and total proteins. Corrected serum total calcium (cTCa) levels were calculated using albumin and total serum calcium levels. In tumour tissues and intact skin, calcium was assayed by physical methods of analysis: Instrumental Neutron Activation Analysis (INAA), Proton-Induced X-ray Emission (PIXE). Intact PTH was measured by ELISA. PTH-independent hypercalcaemia prevalence is low in SCC patients (1.21%). Hypercalcaemia manifestations are multiple including: digestive, renal, neuromuscular, and cardiovascular abnormalities. In these patients, intact PTH (iPTH) is normal, urinary calcium is decreased, serum albumin is reduced, and calcium concentration in tumour tissue is significantly increased compared to healthy tissue. PTH-independent hypercalcaemia has a low prevalence in SCC patients. Hypercalcaemia is correlated with susceptibility to develop metastases in SCC. A possible mechanism is PTHrp hypersecretion by malignant keratinocytes.