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<b><i>Background:</i></b> Medullary thyroid carcinoma (MTC) comprises 1–2% of all thyroid cancers, yet 15% of all thyroid cancer-related deaths. While up to 20% of cases may be predicted due to autosomal dominant germline mutations, 80% of cases are sporadic. However, due to non-specific presenting symptoms and diagnostic imaging, prompt diagnosis and treatment has remained elusive. This article will further investigate the limitations of MTC diagnosis and look into future areas for diagnostic improvement. <b><i>Methods:</i></b> Relevant articles were identified using a systematic PubMed and Google Scholar search. <b><i>Results:</i></b> Prophylactic total thyroidectomy for the 20% of MTC cases that are present in autosomal dominant disorder provides definitive treatment. Serum calcitonin (Ctn) screening has several technical limitations due to population variability and laboratory assay interference, but advances in laboratory technology and combined use with fine needle aspiration increase its sensitivity. Other serum assays such as carcinoembryonic antigen and procalcitonin have limited applicability. Thyroid ultrasound remains the gold standard for the initial diagnostic planning, with limited application for CT, MRI, and PET imaging. <b><i>Conclusion:</i></b> With complete surgical resection the only definitive treatment, early MTC diagnosis has presented an elusive challenge, mainly due to its relative rarity and difficulty in finding an economic screening strategy. Careful family history combined with fine needle aspiration with serum Ctn analysis can improve diagnostic sensitivity and specificity to greater than 95%.

Background Familial hypocalciuric hypercalcemia (FHH) causes hypercalcemia via inactivating genetic mutations in the calcium-sensing receptors of parathyroid cells. FHH generally presents as a chronic, mild, asymptomatic hypercalcemia (&lt;12mg/dL) with normal to moderately-elevated serum PTH levels. Low renal calcium/creatinine clearance ratio (CCCR) is the primary biochemical method of distinguishing FHH from primary hyperparathyroidism (PHPT). Most patients do not require treatment. Surgery is generally inappropriate as hypercalcemia persists after subtotal parathyroidectomy. Clinical Cases A 19-year-old male was admitted to the psychiatry service due to suicidal ideation. He denied taking any medications or supplements. Initial labs noted a corrected calcium of 11.6 mg/dL (ref. 8.6-10.2 mg/dL) and repeat labs verified hypercalcemia. Intact PTH level was 118.8 pg/mL (ref. 15-65 pg/mL). He denied muscle weakness, fatigue, joint pain, constipation, kidney stones, or increased thirst. After IV-fluid repletion, his calcium remained elevated. Serum calcium was measured as high as 13.1mg/dL, corrected calcium was as high as 12.5 mg/dL, and ionized calcium was 6.9 mg/dL (ref. 4.5-5.6 mg/dL). 24-hour urine calcium was 93.6 mg/24-hr and CCCR was 0.29%. A presumptive diagnosis of FHH was made, based on the elevated calcium and PTH, with CCCR &lt; 1%. His mood improved and he was discharged by psychiatry without starting any medications. Initiation of cinacalcet was discussed, but the patient preferred not to start medication. During outpatient follow-up, he did not endorse depression or suicidal ideation. He was referred for genetic analysis to confirm FHH. Due to his significant hypercalcemia, PHPT remained in consideration. Evaluation for MEN syndromes was also performed, since these are associated with early onset PHPT. He knew limited family history. His mother had hypercalcemia and hyperparathyroidism, requiring surgery. He was uncertain of her age at diagnosis or whether she had genetic testing. He also reported a maternal half-brother with hypercalcemia and renal disease, requiring dialysis in his 30s. Repeat labs a few months after his admission showed corrected calcium of 12. 0 mg/dL, ionized calcium of 6.8 mg/dL, and CCCR of 0.30%. Thyroid ultrasound and Tc-99m Sestamibi scan did not show evidence of parathyroid adenoma(s). Genetic analysis showed a known heterozygous pathogenic variant in the CASR gene, consistent with FHH, type 1. The patient continued to deny any symptoms, including psychiatric, and did not start cinacalcet. Conclusion FHH can occasionally present with corrected calcium &gt; 12 mg/dL and PTH &gt;100. CCCR is essential to distinguish FHH from PHPT. Genetic analysis should be pursued in patients with a questionable diagnosis. PHPT is primarily managed with surgery, while FHH is generally not managed with surgery, so correct diagnosis is essential. Rarely, FHH patients may present with pancreatitis, chondrocalcinosis, muscle cramps, poor memory and psychosis. Calcimimetic therapy may be considered in select, symptomatic patients. Presentation: No date and time listed

Introduction Periodic paralysis (PP) is a disorder of muscle ion channels. It is clinically manifested by episodes of painless muscle weakness and often precipitated by heavy exercise, fasting, or high-carbohydrate meals. Although first described in 1951, there is limited information for its long term course. We describe long term follow up of 3 cases of PP. Case 1 A 28-year-old male presented to the emergency room for abnormal sensations of lower extremities and inability to move his legs. Symptoms progressed to upper extremities with serum potassium of 1.7 mmol/L. He was treated with potassium chloride and discharged the next day with diagnosis of PP. He reported high intensity exercise precipitating these episodes and milder symptoms two years previously. Patient also had symptoms of hyperthyroidism, confirmed by thyroid functions tests. Physical examination showed normal vitals, small but palpable thyroid, and no neurological deficit. He was treated with methimazole, propranolol and KCl 20meq. Serum potassium normalized in 4 weeks and KCl was stopped. Following 3 months of treatment, patient developed hypothyroidism and was prescribed levothyroxine. Patient is currently euthyroid and able to perform daily activities without episodes of PP for the next 6 years of follow up. Case 2 A 29-year-old male presented with severe exertional muscle weakness for 1.5 years. Symptoms worsened with exercise. He had no family history of any neurologic diseases. Physical examination: normal vitals, thyroid, muscle, and neurologic exam. Laboratory values: normal thyroid function, serum potassium, liver function, and creatine kinase. EMG showed decreased amplitude of the compound muscle action potential (CMAP), with reduced motor unit recruitment or electrical silence. Patient was prescribed propranolol 20mg. Genetic testing revealed CACNA1S mutation consistent with hypokalemic periodic paralysis. He was prescribed eplerenone and acetazolamide. He has displayed no new symptoms from exertion and continues to perform normal daily activities on the current regimen. Case 3 A 72-year-old male presented with episodes of flaccid paralysis that lasted several minutes. Patient reported each episode started about an hour after eating dinner. During one episode serum potassium was 3.2 mmol/L and his symptoms slowly resolved after receiving potassium. His medical history was notable for hyperlipidemia, hypertension and pre-diabetes. Vital signs revealed stage-1 hypertension. Physical examination during the episode was notable for weakness greater in the proximal muscles and hyporeflexia. Laboratory values with TSH 2.03 mcIU/mL and follow-up potassium level 4.3 mmol/L. He continues to perform normal daily activities without any PP symptoms for the next 9 years following the initial episode. Conclusion Limited information is available regarding the long-term follow up of patients diagnosed with PP. Our 3 patients illustrate a relatively benign long-term course with appropriate treatment. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.