Drug-induced Osteoporosis

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Rare Case of Adult Onset Pompe’s Disease

Pompe’s disease is a lysosomal storage disease characterized by accumulation of glycogen primarily in muscle tissue. Infantile and late onset are the two common forms of this disease. We present a case of adult onset Pompe’s disease in a patient with type 1 diabetes mellitus (DM) with involvement of muscle, liver and bone. A 28-year-old male was being followed up for type 1 DM. He had long standing mild muscle weakness. Family history was significant for unknown muscle disorder in father and cardiomyopathy in grandfather. In addition to elevated CPK levels of 1340 (reference range \u3c 130IU/L) there was elevation of transaminases. A muscle biopsy showed autophagic activity producing rimmed vacuole like structures in the muscle fibers with increased staining of cytoplasm with Periodic acid Schiff. Further work up was delayed due to being busy with college education. Ten years later patient decided to undergo further work up, which showed persistently elevated CPK and transaminase levels. EMG studies showed generalized myopathic process. Serum acid maltase level was found to be low. Genetic testing with acid alpha Glucosidase gene sequencing showed c.-32-13T\u3eG and c.1655T\u3eC (p. L552P) mutation. He was started on enzyme replacement therapy (ERT) with acid maltase infusions, which led to improvement in symptoms, CPK and transaminases levels. Pompe’s disease is a type 2 glycogen storage disease; adult onset is characterized by partial deficiency of enzyme acid maltase. Buildup of the glycogen in Pompe’s disease causes lysosomes to expand leading to muscle damage. Presentation involves limb girdle weakness, respiratory insufficiency, often presents as asymptomatic CPK elevation. Glycogen hepatopathy associated with poorly controlled diabetes and myotonic dystrophy are important differentials to consider in patients with type 1 DM. Patient’s with Pompe’s disease are also found to have increased incidence of low bone density and should be screened periodically with DEXA. Since glycogen hepatopathy is associated with uncontrolled Type 1 DM, tight control of diabetes may help to reduce the impact of acid alpha glucosidase deficiency. Improvement of bone density after ERT suggests need for further studies to elucidate the pathophysiology of bone involvement in this disorder. Late-onset Pompe’s disease is a rare, progressive, autosomal recessive disorder; disease progression and symptomatology are variable between individuals, which often delays the diagnosis. Additional impact of type 1 DM is of concern in our patient. Use of ERT has substantially altered outcomes for the patients, underscoring the importance of early diagnosis with high index of suspicion.https://scholarlycommons.henryford.com/merf2019caserpt/1029/thumbnail.jp

Pneumocystis Carinii Pneumonia: A Rare Cause of Granulomatous Hypercalcemia

Pneumocystis Carinii pneumonia (PCP) is a well-known complication of immunosuppression. Scattered case reports have linked PCP and its ability to induce a granulomatous response to hypercalcemia. PCP related hypercalcemia appears to be resistant to standard therapy. We report a case of hypercalcemia that preceded PCP and continued to worsen during the course of infection. A 63y man with renal transplant for polycystic kidney disease one year prior, presented with a three week history of fatigue, cough and chills. Patient was hypoxic and CT of the thorax revealed diffuse ground glass opacities. He was started on empiric therapy for PCP with intravenous methylprednisolone, clindamycin, and primaquine. Laboratory studies revealed a serum calcium of 12 mg/dl (baseline 9.2mg/dl, reference range 8.6-10.4 mg/dl) and creatinine of 3.23 mg/dl, which rose from a baseline value of 1.6 mg /dl. The patient’s bronchoalveolar lavage confirmed PCP. Endocrinology was consulted for evaluation of hypercalcemia. Further investigations revealed a suppressed PTH of 15 pg/ml from a baseline of 97 pg/ml (reference range 15-65pg/ml) post-transplant, 25-hydroxyvitamin D level of 30 ng/ml (reference range \u3e20 ng/ml ), and 1,25-dihydroxyvitamin D(1,25D) level was elevated (\u3e156 pg/ml; reference range 20-79 pg/ml). A diagnosis of 1,25D mediated hypercalcemia was made, intravenous fluids started and high dose steroids continued. Serum calcium levels improved transiently but subsequently rose to a peak level of 13.5 mg/dl. Ketoconazole 200 mg every 8hrs was started to reduce 1,25D production. Serum calcium remained high despite a reduction in 1,25D level (33 pg/ml). Bisphosphonates therapy was considered unsafe because of decreased GFR. Therefore, denosumab 30mg was administered, which resulted in decrease in serum calcium level to 10.3 mg/dl by day 19. Improvement of hypercalcemia correlated with improvement of PCP and renal function. Patient was discharged home after completing the 21 day course of treatment for PCP. Five weeks later, serum calcium stayed normal with an elevated PTH of 153 pg/ml and 1,25D level of 20 pg/ml.Hypercalcemia heralding PCP infection has been reported in the literature. Elevated calcium of 10.6 mg/dl was present one month prior to our patient’s hospitalization around the time of onset of his symptoms. Of the 19 cases of hypercalcemia due to PCP infection, 5 had hypercalcemia that preceded PCP infection by few weeks. The gold standard for diagnosis of PCP involves identification of the organism in induced sputum or bronchoalveolar lavage specimen. Measurement of serum 1,3-β-d-Glucan, which has high sensitivity, may be used as a screening tool in the right clinical setting such as our patient with immunosuppression and hypercalcemia to diagnose PCP at an earlier stage. We believe that hypercalcemia in a patient with immunosuppression should alert the possibility of PCP infection.https://scholarlycommons.henryford.com/merf2019caserpt/1027/thumbnail.jp

Bone Nanomechanical Properties and Relationship to Bone Turnover and Architecture in Patients With Atypical Femur Fractures: A Prospective Nested Case-Control Study

Atypical femur fractures (AFFs) are well-established serious complication of long-term bisphosphonate and denosumab therapy in patients with osteopenia or osteoporosis. To elucidate underlying mechanism(s) for the development of AFF, we performed a nested case-control study to investigate bone tissue nanomechanical properties and prevailing bone microstructure and tissue-level remodeling status as assessed by bone histomorphometry. We hypothesized that there would be differences in nanomechanical properties between patients with and without AFF and that bone microstructure and remodeling would be related to nanomechanical properties. Thirty-two full-thickness transiliac bone biopsies were obtained from age- and sex-matched patients on long-term bisphosphonate therapy with (n = 16) and without an AFF (n = 16). Standard histomorphometric measurements were made in each sample on three different bone envelopes (cancellous, intracortical, and endosteal). Iliac bone wall thickness was significantly lower on all three bone surfaces in patients with AFF than in those without AFF. Surface-based bone formation rate was suppressed similarly in both groups in comparison to healthy premenopausal and postmenopausal women, with no significant difference between the two groups. Nanoindentation was used to assess material properties of cortical and cancellous bone separately. Elastic modulus was higher in cortical than in cancellous bone in patients with AFF as well as compared to the elastic modulus of cortical bone from non-AFF patients. However, the elastic modulus of the cancellous bone was not different between AFF and non-AFF groups or between cortical and cancellous bone of non-AFF patients. Resistance to plastic deformation was decreased in cortical bone in both AFF and non-AFF groups compared to cancellous bone, but to a greater extent in AFF patients. We conclude that long-term bisphosphonate therapy is associated with prolonged suppression of bone turnover resulting in altered cortical remodeling and tissue nanomechanical properties leading to AFF

Neuroblastoma Masquerading as Pheochromocytoma

Peripheral neuroblastic tumors (PNTs) are a group of tumors arising from sympathetic ganglion cells. It is a malignancy of childhood and rare in adults. The incidence in adulthood is only 0.12-0.2 cases per million per year. A 37 year old male presented with acute exacerbation of low back pain which started months prior to admission. MRI of the lumbar spine revealed a 3.6 x 3.4 cm lobulated heterogeneous mass-like lesion involving his right adrenal gland therefore, endocrinology evaluation was requested but not completed. He was a non-smoker without any significant past medical or surgical history and was not on any medications.On examination, He was normotensive and appeared to be in moderate distress. He had tenderness over the right sacroiliac joint. His renal and liver functions were normal. Serum metanephrines were normal however, normetanephrines were elevated to 501 pg/mL (\u3c or = 148 pg/mL). Urine normetanephrines were 3,192 ug/day (88-444 ug/d), Urine volume of 3 L, total metanephrines of 3,342 ug/d (140-785 ug/d). Chromogranin A was 1,379 ng/mL (0-95 ng/mL). DHEAS, 17- hydroxyprogesterone, androstendione, and ACTH were normal. CT of his abdomen and pelvis with contrast showed a lobular heterogeneous mass involving the right adrenal gland with an increased size of 4.9 x 4.3 cm measuring 55 Hounsfield Units (HU). Right iliac core needle biopsy was done to evaluate his diffuse osseous metastasis which showed crush artifact, with positive chromogranin and synaptophysin staining. Right posterior pelvic crest lesion excision biopsy showed primitive small round cell neoplasm with neuroendocrine features, favoring an adult type neuroblastoma confirmed by immunohistochemical staining. He received chemotherapy and radiation and prior to debulking surgery, we initiated doxazosin. Surgery revealed a 6 cm neuroblastoma with extraadrenal extension. Iodine 123-metaiodobenzylguanidine (I-123 MIBG) showed extensive diffuse osseous metastatic disease. His catecholamines declined after surgery. Bone marrow (BM) involvement was noted and he underwent bone marrow transplantation with clinical improvement six months post-transplant. Although pediatric neurblastoma has a 91% survival rate, rates progressively decline to 40% in adults aged 25-64 years. Metastatic dissemination occurs in up to 40% of adults, mainly in the bone and BM as seen in our case therefore, adults should have a BM assessment upon diagnosis. Main issue is differentiation between PNTs and pheochromocytoma, that might be challenging due to variable imaging characteristics of PNTs and secretion of catecholamines in up to 70% of PNTs. On the other hand, catecholamines can be used as tumor markers for monitoring. Majority of adult PNTs are high-risk tumors with poor prognosis. No guidelines for adult management exists due to the rarity of the disease.https://scholarlycommons.henryford.com/merf2019caserpt/1028/thumbnail.jp