Faculty Bibliography

Background Parathyromatosis, described as hyperfunctioning, benign parathyroid tissue scattered throughout the soft tissues of the neck, is a rare cause of recurrent hyperparathyroidism. Fewer than 40 cases have been described in the literature. We describe a case of a woman with recurrent hypercalcemia secondary to parathyromatosis; additionally this is the first reported case of a papillary pattern in parathyromatosis. Clinical Case A 45 year old woman with a history of a left parathyroid adenoma, status post focused parathyroidectomy 10 years ago, presented with constipation, polyuria and abdominal pain. Initial examination demonstrated a well healed cervical scar with no palpable neck masses. Admission laboratory findings were significant for a calcium level of 13.6 mg/dL (n 8-10.4 mg/dL) , ionized calcium 7.7 mg/dL (n 4.6-5.2 mg/dL), phosphorus 2.2 mg/dL (n 2.7-4.5 mg/dL), 25 OH-vitamin D 9.6 ng/mL (n 30-100 ng/mL), PTH 395 pg/mL (n 14-72 pg/mL), PTHrP <0.7 pmol/L (n <2.0 pmol/L) and urine calcium 484 mg/24 hr (n 50-250 mg/24hr). No obvious enlarged parathyroid was localized on neck ultrasound or sestamibi scan. Neck CT showed two 6 mm nodular lesions in the upper mediastinum. The patient had refractory hypercalcemia despite maximal medical therapy. She was taken to the operating room for reoperative neck exploration. She was noted to have diffuse exophytic fronds of tissue covering her left thyroid lobe, which prompted removal of the lobe. Intraoperative PTH decreased from 454 pg/mL to 39 pg/mL. Microsopic examination demonstrated multifocal hypercellular parathyroid nodules in skeletal muscle and perithyroid adipose tissue consistent with parathyromatosis. An unusual pathologic finding was its unique papillary configuration, raising consideration for a parathyroid carcinoma on frozen section. Final pathology confirmed parathyromatosis with no features of carcinoma (vascular invasion, fibrosis or high mitotic activity) with diffuse immunohistochemical reactivity for PTH and non-reactivity for Thyroid Transcription Factor-1. The patient's calcium level was normal post operatively (9.2 mg/dL) with resolution of symptoms. Conclusion Parathyromatosis is a rare disease that raises challenges in diagnosis and management. Preoperative localization of parathyromatosis is difficult, leading to a high surgical failure rate. Scarring and fibrosis from previous neck exploration leads to technical difficulty, since the most common cause for parathyromatosis is seeding of hypercellular parathyroid tissue during previous parathyroidectomy. Medical management is essential during the post-operative period to maintain a normocalcemic state. Our case presents with a pathologic finding of papillary pattern in parathyromatosis, which has not been previously described and can pose a diagnostic challenge in separation from papillary carcinoma on frozen section examination

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent condition. Emerging evidence suggests that vitamin D may play a role in the pathogenesis of NAFLD. AIM: To review systematically the association between vitamin D levels, measured as serum 25-hydroxy vitamin D [25(OH)D], and NAFLD. METHODS: We used PubMed and EMBASE databases to identify all studies that assessed the association between vitamin D and NAFLD up until 22 April 2013, without language restrictions. We included studies that compared vitamin D levels between NAFLD cases and controls and also those that compared the odds of vitamin D deficiency by NAFLD status. Pooled standardised differences and odds ratios were calculated using an inverse variance method. RESULTS: Seventeen cross-sectional and case-control studies have evaluated the association between vitamin D and NAFLD. NAFLD was diagnosed using biopsy (4 studies), ultrasound or CT (10 studies) and liver enzymes (3 studies). Nine studies provided data for a quantitative meta-analysis. Compared to controls, NAFLD patients had 0.36 ng/mL (95% CI: 0.32, 0.40 ng/mL) lower levels of 25(OH)D and were 1.26 times more likely to be vitamin D deficient (OR 1.26, 95% CI: 1.17, 1.35). CONCLUSIONS: NAFLD patients have decreased serum 25(OH)D concentrations, suggesting that vitamin D may play a role in the development of NAFLD. The directionality of this association cannot be determined from cross-sectional studies. Demonstration of a causal role of hypovitaminosis D in NAFLD development in future studies could have important therapeutic implications.

Hypercalcemia is often a clue to the presence of unsuspected illness. We present an interesting case of an HIV-positive transgender female with a rare cause of silicone-induced granulomatous hypercalcemia. Although there have been a few case reports of silicone injections in dialysis patients causing hypercalcemia, this metabolic derangement secondary to silicone granulomas continues to be a unique entity with an unclear pathophysiology. We present a 45-year-old transgender HIV-positive female, with extensive silicone injections, who presented with symptomatic hypercalcemia. Workup for malignancy and hyperparathyroidism was negative. 1,25-Dihydroxyvitamin D level and 24-hour urine calcium level were elevated. CT scan showed extensive high-density reticulonodular densities in the buttocks and gluteal muscle fascia extending upwards to the lumbar region, along with prominent external iliac and inguinal lymph nodes. Nuclear imaging showed diffuse heterogeneity and increased uptake in the buttocks, most consistent with granuloma calcifications, and an inguinal lymph node biopsy confirmed a foreign body giant cell reaction. The patient was started on prednisone and this resulted in decrease in serum and urinary calcium levels. Physicians should have a high index of suspicion for silicone-induced hypercalcemia considering the growing prevalence of body contour enhancement with injections, implants, and fillers using this material.

Hepatic epitheliod hemangioendothelioma (HEHE) is a rare tumor of vascular origin with unpredictable malignant potential. We describe our experience with four biopsy-proven HEHE cases that were considered for orthotopic liver transplant (OLT). Three patients had preserved hepatic function and despite extensive disease burden did not develop disease progression while awaiting OLT. We were able to utilize the review process allowed by United Network of Organ Sharing to obtain additional priority for OLT for these patients. This led to expedited organ allocation and excellent post-OLT outcomes.