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Case: A 57 year old man with squamous cell carcinoma (SCC) of the tongue with complete response to chemoradiation was found unresponsive with a reading of “low” by a POC glucometer. He was treated with an IV dextrose bolus but had recurrent hypoglycemia requiring a continuous dextrose infusion. He was diagnosed with COVID-19 pneumonia, acute hepatitis (elevated liver enzymes), and acute kidney injury (elevated serum creatinine 1.2 mg/dL). Other labs: elevated TSH 8.44 uIU/mL, normal AM cortisol 16.4 ug/dl. A 5.1 cm mass was discovered in the left lung with bilateral nodules, biopsi revealed SCC of unclear origin (either lung or metastatic disease from prior tongue cancer). He was malnourished from prior cancer related dysphagia and nutritional supplements were added. Despite this and improvement in liver and kidney function, he had persistent hypoglycemia. He became hypoglycemic within 4-hrs while performing a 72-hr fast with labs: serum glucose 45 mg/dL, insulin < 2 uU/mL, c-peptide < 0.1 ng/mL, proinsulin < 4 pmol/L, beta hydroxybutyrate 0.17 mmol/L, IGF1 < 16 ng/mL (ref: 50 - 317), IGF2 147 ng/mL (ref: 267-616), negative hypoglycemia panel and insulin antibody. This was consistent with a paraneoplastic hypoglycemia known as non-islet cell tumor hypoglycemia (NICTH). To discontinue the dextrose infusion, he was started on prednisone 20 mg daily titrated up to 60 mg daily, intermittent tube feeds and palliative chemotherapy. With this, hypoglycemia improved, and the dextrose infusion was discontinued. Unfortunately, he had ischemic bowel perforation leading to cardiac arrest and death. Discussion: Our patient had NICTH as suggested by the 72-hr fast (non-insulin mediated hypoglycemia, IGF2/IG1 ratio > 10) and the presence of a tumor. It is mediated by tumor-produced IGF-2 causing increased glucose utilization, decreased gluconeogenesis, glycogenolysis and ketogenesis. Curiously, IGF-2 may not be elevated if the tumor produces a partially processed “big IGF-2” for which there is no commercial assay. Instead, an IGF2/IGF1 ratio close to or more 10 is indicative of NICTH. Mesenchymal and hepatic tumors are the most common cause of this rare entity with an incidence of one per million people years. A literature search showed very few reports of SCC-mediated-NICTH, with one case of esophageal SCC. Our patients’ primary tumor was undetermined (lung vs tongue) - but in either case this could be a novel association. A multidisciplinary approach is required centered around the tumor (surgery, chemotherapy, or radiation). High dose prednisone 30 to 60 mg daily can be used in the interim as it decreases IGF-2 but is not always successful. Recombinant hGH and glucagon are alternatives or can be combined with steroids. In summary IGF2/IGF1 ratio should be calculated, palliative tumor directed therapy should be initiated with prednisone and supplemental nutrition as adjuncts.

Introduction: Bone metastases from differentiated thyroid cancer are generally resistant to radioactive iodine (RAI) therapy and are associated with poor prognosis, except for RAI-avid bone metastases with no structural correlate on imaging studies. Case: A 59 y/o woman presented for the evaluation of non-toxic multinodular goiter. Thyroid US showed a 2.7 cm nodule meeting FNAB criteria and no suspicious cervical lymph nodes. Cytology reported a Bethesda IV category with ThyroSeq V3 positive for chromosomal copy number alterations and a high Na+/I− symporter (NIS) expression (27%) with an ~ 60% probability of cancer. The patient underwent left lobectomy with isthmusectomy without neck dissection. Surgical pathology showed a 3.5 cm papillary thyroid carcinoma with extensive angioinvasion (≥4 vessels), negative margins, no ETE, and did not contain a BRAF V600E mutation. Completion thyroidectomy, in anticipation of RAI treatment, showed no additional tumor. Post-operative Tg after 6 weeks was unexpectedly high at 69 ng/mL (negative Tg Ab, TSH 5.7 uIU/ml) which prompted a rhTSH I-123 RAI WBS with SPECT/ CT and a diagnostic chest CT to uncover possible distant metastases. There was RAI uptake in the thyroid bed and right anterolateral 9thrib without a CT correlate (no osteolytic lesion) but with a signal abnormality on MRI. She was categorized as T2NxM1, 8th Edition AJCC Stage IVB, and ATA high risk. She was treated with 148.3 mCi I-131. Unfortunately, 6 months later the Tg was elevated and rising (Tg 38.4 ng/mL, negative Tg Ab, TSH 0.05 uIU/ml). A second diagnostic I-123 WBS with SPECT/ CT showed a new recurrence in the neck but no uptake in the rib lesion on planar images or other distant sites. Because of the unusually high Tg without any RAI-avid metastatic disease, an 18-FDG PET/CT was ordered to search for non-RAI avid disease. This showed disease confined to the neck and increased sclerosis of the rib lesion without increased FDG-uptake consistent with treated disease status post-RAI. There were no other distant hypermetabolic lesions. The left thyroid bed lesion was biopsied and consistent with Bethesda VI cytology and she will soon undergo left central neck dissection with tumor resection. Discussion: RAI-avid bone metastases without structural correlate on high-resolution imaging are a subtype of bone metastases located in the marrow. They do not present as the typical lytic lesions from cortical destruction. They often resolve following RAI treatment, do not cause skeletal-related complications, and do not significantly affect prognosis. The combination of high NIS expression and increased vascularity in the bone marrow (as opposed to the protected microenvironment in the bone cortex) makes them vulnerable to RAI treatment. Recognition of this subset of bone lesions may prevent overtreatment with high doses of RAI treatment and avoid the use of bisphosphonates or external beam radiation.

Introduction: Parathyroid carcinoma (PC) is a rare malignancy with a high rate of recurrence and metastasis. Case: A 63-year-old man with a 13-year history of recurrent PC requiring 5 operations, including parathyroidectomies, thyroidectomy, and neck dissections presented with polyuria, polydipsia, and worsening rib pain. He had been recently treated with 6 monthly octreotide injections and maximal dose cinacalcet for gradually rising Ca/PTH levels. Tests revealed serum Ca 13.1mg/dL (8-10.5mg/dL), PTH 1750pg/mL (11-90 pg/mL), and serum Cr 3.34mg/dL (0.5-1.3mg/dL). Imaging identified tumor in the right 6th rib (3.6cm lytic lesion), and soft tissue lesions in the left thyroid bed (3 masses, the largest 1.6cm) and the suprasternal notch (1.1cm). He underwent rib resection (metastasectomy) and PTH declined from 2334pg/mL to 671pg/mL. Although metastasectomy improved the PTH level, Ca levels began to rise from the residual tumor. A multidisciplinary team deemed the risk of complications from repeat neck surgery to be prohibitively high. Temozolomide (TEM) (150-200mg/m2/d x 5d, q28d) was instituted 3 months after the rib resection. 13 months later, PTH has stably ranged from 600-800 pg/mL with a normal serum Ca of 9.8mg/dL. Recent imaging shows stable disease in the neck, without distant disease. Discussion: The mainstay of therapy for initial and recurrent/metastatic PC is surgery. Inoperable disease has a poor prognosis because of lack of effective systemic therapies. Radiation and chemotherapy have not shown much efficacy. Results of treatment with octreotide have not been encouraging. Anti-PTH immunotherapy and Lutathera are promising but require further investigation. Usually, no targetable mutation is found. Anti-angiogenic TKI’s (sorafenib, lenvatinib) have been used with varying success. An exciting therapy used in this patient is TEM, an alkylating agent used for CNS tumors, neuroendocrine tumors (NET) and aggressive pituitary tumors. A previous report described successful use of TEM in a case of metastatic PC, whose tumor harbored high O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, a known predictor of positive response in CNS tumors. Promoter methylation is an epigenetic alteration that leads to low MGMT enzyme activity & enhances the cytotoxicity of TEM. Some studies in NET demonstrated tumor response irrespective of MGMT status. This leads to the question of whether the same is true in PC. Our patient has radiographic/biochemical stable disease on TEM, and a surprising retrospective discovery was that the MGMT promoter was unmethylated. This is a unique case of PC which seems to be responding to TEM despite absent promoter methylation. Further studies are warranted, as the incidence of PC is rising over the past decades. In the interim, clinicians could consider using TEM for in-operable PC irrespective of MGMT methylation status.

A major surgical procedure results in injury resulting in systemic response resulting in a negative nitrogen balance. The conventional management of a patient in the peri-operative period involves pre- and post-operative fasting, which potentiates the caloric deficit. Early feeding has been shown to result in a positive clinical outcome. However, the physiologic response to surgery impedes successful initiation of early enteral feeds. This article discusses the various strategies to improve tolerance to early enteral feeds in the immediate post-operative period.