Faculty Bibliography

BACKGROUND/OBJECTIVE/UNASSIGNED:To report a case of recalcitrant post-surgical hypocalcemia caused by hypoparathyroidism complicated by a chyle leak and octreotide use. CASE REPORT/UNASSIGNED:A man in his 60s with a 4-month history of voice changes, 10-pound weight loss, and a right-sided neck mass presented with difficulty breathing for 1 week. He had a right laryngeal/hypopharyngeal mass, which was biopsied. Pathology results were positive for invasive squamous cell carcinoma. He underwent an extensive neck surgery, including total thyroidectomy. Postsurgical laboratory results revealed serum corrected calcium of 7.6 mg/dL (ref 8.0-10.2 mg/dL) and parathyroid hormone <6.3 pg/mL (ref. 10-65). Despite treatment with calcium carbonate 12 g (elemental) daily, calcitriol and hydrochlorothiazide, his corrected serum calcium levels remained low. Patient also had a chyle leak that was treated with octreotide. Resolution of his hypocalcemia occurred after substitution of calcium carbonate with calcium citrate, cessation of octreotide, and management of the chyle leak. DISCUSSION/UNASSIGNED:Our patient likely developed recalcitrant hypocalcemia from: 1) postsurgical hypoparathyroidism, 2) a chyle leak, and 3) the use of octreotide. Administration of octreotide to seal the chyle leak most likely decreased gastric acid production and contributed to decrease in absorption of calcium carbonate. Oral calcium citrate may be better absorbed in this case. CONCLUSION/UNASSIGNED:Postsurgical hypoparathyroidism can lead to hypocalcemia. This case is unique in that the patient's chyle leak and the use of octreotide contributed to recalcitrant hypocalcemia.

Context/UNASSIGNED:Thyroid hormone plays a critical role in cardiovascular function. Severe hypothyroidism can be associated with "myxedema heart" characterized by relative bradycardia and pericardial effusion. Effusions associated with severe hypothyroidism can be large. Despite the large volume of effusions, tamponade is not a common consequence. However, with the incorporation of echocardiography into routine practice for evaluation of effusion, echocardiographic findings suggestive of clinical tamponade occur frequently. Case Description/UNASSIGNED:We report a series of 3 patients with large pericardial effusions secondary to severe hypothyroidism. These cases serve to demonstrate the discordance between echocardiographic signs consistent with tamponade with a patient's stable clinical hemodynamics. We also report the development of bronchial obstruction, a rare complication of a large effusion due to severe hypothyroidism. Conclusions/UNASSIGNED:While pericardial effusion associated with severe hypothyroidism has been described for decades, the echocardiographic findings may be less well known and may lead to unnecessary downstream testing or invasive management. We use our case series to facilitate a summary of what is known about the epidemiology, mechanism and physiology, and expected outcomes of myxedema associated pericardial effusion. Finally, in the setting of current paucity of clinical guidelines, we aim to familiarize clinicians with the phenomenon of pseudotamponade and suggest management strategies for myxedema associated pericardial effusion to guide clinicians to use conservative medical management in majority of cases.

We present a case of recalcitrant post-surgical hypocalcemia caused by hypoparathyroidism further complicated by a chyle leak and treatment with octreotide. A 60-year-old man with 4 months of hoarseness, 10-poundweight loss, and right-sided neck mass presented with difficulty breathing for one week. Imaging showed a right laryngeal/ hypopharyngeal mass. Pathology results revealed an invasive squamous cell carcinoma. He underwent an extensive neck surgery, which included a total thyroidectomy with parathyroidectomy. Post-operative day 1, laboratory results revealed a corrected calcium of 7.6 mg/dL [8.0-10.2], magnesium of 1.2 mg/dL [ref 1.3-1.9], phosphorus of 5.3 mg/dL [2.7-4.5], parathyroid hormone of <6.3 pg/ mL, 25-hydroxyvitamin D level was 13.1 ng/mL. Patient denied symptoms of perioral numbness, tingling of extremites, or muscle cramping. Despite treatment with elemental calcium carbonate 12 grams daily, calcitriol 0.50 mcg daily, HCTZ 12.5 mg daily via PEG, his serum calcium levels remained low at 7.6 mg/dL. He required recurrent management with intravenous calcium gluconate. His severed throacic duct caused by a chyle leak was treated with octreotide 100 mg subcutaneously three times a day. Calcium carbonate was switched to calcium citrate 1900 mg three times a day to increase calcium absoprtion. The patient's chyle leak eventually resolved, octreotide was stopped, and his serum calcium further improved off of IV calcium. His calcium improved to 9.5 mg/dL and he was discharged with oral calcium citrate, calcitriol, and cholecalciferol. Extensive neck surgery caused hypoparathyroidism and a chyle leak, both contributing to hypocalcemia. Chyle contains calcium and fat soluble vitamin D. Octreotide decreases chyle flow and suppresses gastrointestinal hormones such as gastrin, decreasing the acid environment optimal for calcium carbonate absorption. The use of calcium citrate which is absorbed independently of gastric acidity, the resolution of the chyle leak, and the cessation of octreotide improved serum calcium levels. Post-surgical hypoparathyroidism can lead to hypocalcemia. This case is unique in that chyle leak and use of octreotide contributed to recalcitrant hypocalcemia

The proper clinical evaluation of pituitary and adrenal disorders depends on the accurate measurement of plasma ACTH. The modern two-site sandwich ACTH immunoassay is a great improvement compared with older methods but still has the potential for interferences such as heterophile antibodies and pro-opiomelanocortin (POMC) and ACTH fragments. We report the cases of five patients in whom the diagnosis or differential diagnosis of Cushing syndrome was confounded by erroneously elevated results from the Siemens ACTH Immulite assay [ACTH(Immulite)] that were resolved using the Roche Cobas or Tosoh AIA [ACTH(Cobas) and ACTH(AIA), respectively]. In one case, falsely elevated ACTH(Immulite) results owing to interfering antibodies resulted in several invasive differential diagnostic procedures (including inferior petrosal sinus sampling), MRI, and unnecessary pituitary surgery. ACTH(Cobas) measurements were normal, and further studies excluded the diagnosis of Cushing syndrome. In three cases, either Cushing disease or occult ectopic ACTH were suspected owing to elevated ACTH(Immulite) results. However, adrenal (ACTH-independent) Cushing syndrome was established using ACTH(AIA) or ACTH(Cobas) and proved surgically. In one case, ectopic ACTH was suspected owing to elevated ACTH(Immulite) results; however, the ACTH(Cobas) findings led to the diagnosis of alcohol-induced hypercortisolism that resolved with abstinence. We have concluded that ACTH(Immulite) results can be falsely increased and alternate ACTH assays should be used in the diagnosis or differential diagnosis of clinical disorders of the hypothalamic-pituitary-adrenal axis.

The incidence of pericardial effusion in hypothyroidism is 3% in the earlymild stage and up to 80%in patients with myxedema.We present three cases of severe hypothyroidism causing cardiac tamponade. CASE 1. 61-year-old woman with Hashimoto's thyroiditis who initially presented with generalized muscle weakness, found to have a large pericardial effusion with tamponade physiology. Initial labs revealed TSH 198.74 and FT4 < 0.10. Pericardiocentesis was done draining 1.5 L of fluid. CASE 2. 63 year-old woman with no past medical history presented after a mechanical fall, found to have an acute basal ganglion ischemia. TTE was obtained to complete CVA work-up revealing a large pericardial effusion with with tamponade physiology. labs were notable for a TSH 47. CASE 3. 66 year-old woman with hypothyroidism presented with lethargy and dyspnea. TTE revealed large pericardial effusion with tamponade physiology. CT chest revealed a large pericardial effusion that was narrowing the distal left mainstem and left lower lobe bronchi. Pericardiocentesis was done draining 1.1 L of fluid. Pericardial effusion in hypothyroidism is due to increased capillary permeability and impaired lymphatic drainage with subsequent leakage of fluid rich proteins and glycosaminoglycans into the interstitial space. Factors affecting capillary permeability include absence of FGF signaling and decrease in adrenomedullin, resulting in destabilization of the VE-cadherin/b-catenin complex at the cell-cell junctions. There has been no correlation with TSH levels and the existence of effusion. Clinical symptoms of tamponade are uncommon due to slow accumulation of fluid and pericardial distensibility. It is hypothesized that heart rate is within normal range or bradycardic due to decrease sympathetic activity. The color of the fluid is most commonly straw-colored or gold. And the cells are predominantly lymphocytes. The treatment should be individualized. The effusion can be reversed only with levothyroxine because the slow rate of accumulation. Pericardiocentesis is only done when there is hemodynamically instability. Cardiac tamponade presenting with normal or low heart rate with high TSH is highly suggestive of hypothyroidism as the culprit

Radioactive iodine (131I) is used effectively for the treatment of differentiated thyroid cancers. Because it is actively secreted by the salivary glands, radiation damage to these glands can occur. Obstructive swellings after mealtime salivary stimulation are common occurrences. Dry mouth is not usually seen if low doses of 131I are used. A subjective complaint of xerostomia in a patient treated with 131I 75.8 mCi proved to be related to the simultaneous presence of Sjogren syndrome (SS). Serologic, histologic, scintigraphic, and salivary volume findings and the patient's subjective complaints served to establish the pre-existence of SS.

Transient osteoporosis of the hip (TOH) is a temporary clinical condition of unknown etiology which usually resolves with conservative therapy though may be complicated by fracture or progression to avascular necrosis (AVN). TOH may be slightly more prevalent in men but when it occurs in women, it is most often seen in the latter part of pregnancy. Though fracture is a rare complication of TOH when it occurs, it is most often associated with TOH occurring in pregnancy. Magnetic resonance imaging (MRI) is the best method to diagnosis TOH. Low signal intensity on T1-weighted images, high signal intensity on T2-weighted images, and homogenous pattern of edema (the femoral head and/or neck) with normal subchondral area are in favor of TOH. A shortened course to recovery is reported by use of bisphosphonates, calcitonin, or teriparatide. Based on reported cases, core decompression is not superior to medical therapy. Transient osteoporosis of the hip, which often has no known etiology, usually resolves with conservative therapy but may predispose the patient to fracture or avascular necrosis. Diagnostic method of choice is magnetic resonance imaging. Bisphosphonates, calcitonin, or teriparatide are reported as a useful approach to reduce duration of recovery.

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.