Faculty Bibliography

Disease Overview: Clonal, neoplastic proliferation of abnormal mast cells (MC) results in Systemic Mastocytosis (SM) when mast cells are found in one or more organ systems other than skin Presence of multifocal clusters of abnormal mast cells is major criteria for diagnosis. Elevated serum tryptase, abnormal MC expression of CD25 and/or CD2, and presence of KIT D816V mutation are minor criteria for diagnosis. Manifestation and Diagnosis: SM manifestations are attributed to the degree of mast cell proliferation, activation and degranulation. SM has a variable prognosis and presentation, from indolent to "smoldering" to life-threatening disease. Bone manifestations of SM include: osteopenia with or without lytic lesion, osteoporosis with or without atraumatic fracture, ostoesclerosis, and isolated lytic lesion. Male sex, older age, higher bone resorption marker, lower DKK1, lower BMD, absence of urticaria pigmentosa, and alcohol intake are associated with fracture. Table 1. Studies reporting fracture rate and risk factors in patients with mastocytosis in order of the year of publication Treatment: Treatment of SM is generally palliative. Most therapy is symptom-directed; and, infrequently, chemotherapy for refractory symptoms is indicated. Antihistamines may alleviate some of the direct bone effects of histamine. Bisphosphonates including alendronate, clodronate, pamidronate and zoledronic acid are recommended as a first line treatment of SM and osteoporosis. Interferon alpha may act synergistically with bisphosphonates. Since elevations of RANKL and OPG have been reported in SM, denosumab might be effective for bone manifestations of SM

Systemic Mastocytosis (SM) is characterized by accumulation of clonal, neoplastic proliferations of abnormal mast cells (MC) in one or more organ system other than skin. Presence of these multifocal clusters of abnormal mast cells is an essential feature of SM. Frequently associated with D816V (KIT) mutation, the presence of this mutation and elevated serum tryptase are minor criteria for diagnosis. SM manifestations depend on the degree of mast cell proliferation, activation and degranulation. SM has a variable prognosis and presentation, from indolent to "smoldering" to life-threatening disease. Bone manifestations of SM include: osteopenia with or without lytic lesions, osteoporosis with or without atraumatic fracture, osteosclerosis with increased bone density, and isolated lytic lesions. Male sex, older age, higher bone resorption markers, lower DKK1 level, lower BMD, absence of urticaria pigmentosa, and alcohol intake are all associated with increased risk of fracture. Treatment of SM is generally palliative. Most therapy is symptom-directed; and, infrequently, chemotherapy for refractory symptoms is indicated. Anti-histamines may alleviate direct bone effects of histamine. Bisphosphonates, including alendronate, clodronate, pamidronate and zoledronic acid are recommended as a first line treatment of SM and osteoporosis. Interferon alpha may act synergistically with bisphosphonates. As elevation of RANKL and OPG is reported in SM, denosumab could be an effective therapy for bone manifestations of SM.

Significant barriers to informed consent surround the clinical management of adult patients with well-differentiated thyroid cancer. The literature reveals lack of disclosure surrounding clinical equipoise; confusing and conflicting terminology; and an insufficient number of prospective trials with proper ethical oversight. We provide guidance for valid consent to treatment in this population, and propose stipulative definitions for a variety of terms used in this context. Three critical areas are addressed: surgical management, radioactive iodine management and nonvalidated practice. Sound ethical frameworks for valid consent in patients with low-risk thyroid cancer include consent to observational (or 'active surveillance') research protocols, consent to nonvalidated practice and consent when there are opposing standards of care due to insufficient data and disagreement among the community of experts

Testosterone synthesis and male fertility are the results of the perfect coordination of the hypothalamic-pituitary-gonadal axis. A negative feedback finely controls the secretion of hormones at the 3 levels. Congenital or acquired disturbance at any level leads to an impairment of reproductive function and the clinical syndrome of hypogonadism. In some cases, this condition is reversible. Once the diagnosis is made, testosterone replacement therapy is the standard therapy; however, novel therapies may improve spermatogenesis while elevating testosterone levels.

Before the earthquake, Nepal was one of the poorest nations in the world, with 26.5% of its population, or 190 million people suffering from disorders due to iodine deficiency. Glaciation erosion depletes iodine and selenium in soil, leading to deficient iodine in plants and animals. Goats often have large goiters. Selenium deficiency, impairs T4 to T3 conversion and iodine conservation. Water from wells contaminated with toxins including arsenic, mercury and strontium, also contribute to thyroid disease. Iodine deficiency contributes to high rates of pregnancy loss, preterm labor, stillbirth, and neonatal goiter. Nepalese have some of the largest goiters. While neurological cretinism is more common in the world, goitrous cretinism is more common in Himalayan countries such as Nepal. The highest prevalence of thyroid disease is seen in the subjects over the age of 50. Hypothyroidism occurs in 18% of people in some regions of Nepal. Also, hyperthyroidism is more common, occurring in almost 14% of some regions of Nepal. Some studies report that hyperthyroidism is almost as common as hypothyroidism. Most goitrous subjects were euthyroid (58.59%); hyperthyroidism affected (27.38%). Though women still have more thyroid disease than men, the percentage difference is not as great as in other areas of the world. One researcher reported similar prevalence of subclinical hypothyroidism in women and men, alluding to a dominant effect of iodine deficiency being more important than autoimmunity. Men and women with goiters had a similar prevalence of thyroid dysfunction. Iodine deficiency affects iodination. Goats in Nepal show higher MIT/DIT and T3 /T4 ratios. Water contaminants contribute to thyroid disease. Mercury acts as a selenium antagonist. Arsenic interferes with TR binding, transcription, and signaling and increases risk of simple diffuse goiter. Decreasing thyroid disease in Nepal, includes not only supplementation with iodine, but also supplementation with selenium. In addition, avoiding contaminated well water, by using rain water and installing plumbing, is important for improving general health including thyroid disease

First you have a drug, and then you create the perception of need. The diagnosis of osteoporosis determined by bone density testing was promoted in 1995, simultaneously, and not coincidentally, with the FDA approval of the first major drug indicated for osteoporosis treatment. The use of bone density criteria greatly expanded the number of people who might be "diagnosed" to have osteoporosis or low bone density (commonly called "osteopenia") and therefore "eligible" for, or even requiring, medication to treat or prevent osteoporosis. Osteoporosis is a true medical syndrome, but does this make low bone mineral density measurement (BMD) the equivalent? BMD is a surrogate for fracture risk, but it does not have as good a predictive value as other indicators, especially previous fracture or even advanced age. BMD improvement became a standard measure of drug efficacy in many clinical trials rather than the prevention of fracture, the true important outcome. Marketing to and by the medical community, as well as to prospective "patients", has created a huge medical market for a disease that followed the creation of new drugs.

131-I is actively secreted by the salivary glands,causing obstructive symptomatology and hyposalivation. Low dose 131I rarely causes dry mouth but commonly causes post-meal obstructive swelling. Dry mouth in a patient treated with 131-I was due to existing secondary Sjogren's syndrome (SS) exacerbated by RAI. Scintographic, serologic, microscopic findings confirmed secondary SS. Salivary glands concentrate and secrete Technetium-99m pertechnetate (TPT). TPT time/activity scintiscan examines activity of 4 major salivary glands in real-time, distinguishing salivary symptomatology post-131-I from SS. Ductal wall inflammation and blockage following low dose 131-I; scintiscan shows adequate pickup of TPT, but failure to secrete. In contrast, SS causes lymphocytic replacement of entire parenchyma, interfering with acinar cell pickup; scan shows minimal parotid activity. A thyroid cancer patient treated with 131-I showed no parotid activity, pickup or secretion of TPT, but normal submandibular TPT concentration and secretion. Total parotid parenchymal destruction with hyposalivation is more consistent with SS, rather than 131-I effects. Labial microscopy showed focus score = 1 (Chisholm grade 3) lymphocytic clumped foci, consistent with SS. 131-I sialadenitis (Graph presented) causes diffuse lymphocytic distribution. Schirmer test: normal bilateral tear production. Differentiation of dry mouth of autoimmune from radiation sialadenitis is shown by TPT scan. Usually > 150 mCi is required for hyposalivation, and drying effect is not total. Total parotid parenchymal destruction with hyposalivation is more consistent with SS diagnosis

BACKGROUND: We report a case of bilateral adrenal hemorrhage and subsequent adrenal insufficiency after a laparoscopic hysterectomy in a patient with anticardiolipin antibody syndrome. CASE: A 55-year-old woman with a history of anticardiolipin antibody syndrome presented with nausea and vomiting 1 week after laparoscopic hysterectomy and staging for endometrial adenocarcinoma. Based on a diagnosis of adrenal insufficiency, the patient was started on oral hydrocortisone 20 mg in the morning and 10 mg in the afternoon, and fludrocortisone 0.05 mg twice daily on day 5. Her symptoms resolved completely within 24 hours of beginning steroids. CONCLUSION: The diagnosis of adrenal insufficiency should be entertained in any patient with a history of thrombophilias presenting with general abdominal complaints