Prolactin hypersecretion from a pituitary adenoma usually results in a serum prolactin level less than 1,000 ng/ml. During therapy with a dopamine agonist, prolactin levels usually normalize and the tumors shrink substantially. In the past few years, we have seen three men who presented with serum prolactin levels greater than 10,000 ng/ml. All presented with large tumors, visual field deficits, and hypogonadotropic hypogonadism. All other pituitary hormones were normal. In all three patients, significant tumor shrinkage was achieved with improvement or resolution of headaches and visual field deficits. None of our patients has been able to achieve a normal prolactin or testosterone. A literature review identified 32 patients with prolactin levels of more than 10,000 ng/ml. Twenty-six (81%) were males. Most had large tumors, headaches and visual field defects. Even with the addition of surgery and/or radiation therapy to medical therapy, normalization of serum prolactin occurred in only six patients (19%) and only one man achieved a normal testosterone. We conclude that in patients with massive prolactin hypersecretion, therapy with a dopamine agonist will lead to tumor shrinkage and improvement of mass effects, but usually does not normalize prolactin or testosterone. Rather than waiting for maximal prolactin reduction, we would recommend early institution of testosterone replacement therapy.

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Background: 68 Ga-DOTATATE PET-CT (DOTATATE-PET) has higher sensitivity and positive predictive value than other studies, reason for which it has become the imaging modality of choice for Neuroendocrine tumor (NET) localization, but data on ACTH-secreting NET is scarce. Case summary: 61 year old female with history of right hepatic lobe lipoma resection, T2DM (A1c 9.4%), HTN, and benign thyroid nodule that was evaluated for cushingoid features with facial and lower extremity edema, progressive generalized weakness, difficulty climbing stairs, 20 lbs weight loss and intermittent hypokalemia while on a diuretic plus three other antihypertensives over a six month period. ACTH-dependent hypercortisolism was confirmed with a non-suppressed ODST 11.27mcg/dL (normal <1.8), elevated 24 hr urine free cortisol 525 mcg/24h (RR 4.0-50.0, total volume 3.85 L, creatinine 0.92 g/24 hr), midnight salivary cortisol 1.13 mcg/dL(RR ≤0.09), and ACTH 122 pg/mL (RR 6-50). Additionally, plasma metanephrines were negative, aldosterone <1 ng/dl (RR ≤21) and renin activity 0.58 ng/mL/h (RR 0.25-5.82). Cushing’s disease was suspected since her 8am cortisol suppressed >50% after 8 mg dexamethasone (dexa) overnight (pre-dexa cortisol 33.78 mcg/dL, post-dexa cortisol 6.59 mcg/dL). However, MRI Sella did not show a pituitary adenoma and IPSS was compatible with Ectopic ACTH-secretion (EAS). CT chest, abdomen, pelvis with contrast did not reveal any frank lesion that could be the culprit of EAS. Octreoscan and FDG-PET were negative. DOTATATE-PET reported a mild focus of uptake on the medial aspect of the right upper lung lobe, thought to be a branching blood vessel since no anatomic lesion was seen on CT Chest that would correspond to the possible area of uptake. In the interim, she developed diffuse ecchymosis with worsening of her functional status, needing a walker and assistance with activities of daily living. She had several falls complicated by multiple lumbar compression fractures, rib, right pubic ramus and bilateral sacral insufficiency fractures for which she received reclast, a back brace and physical therapy. She was started on ketoconazole and titrated up, but due to rapid progression of her Cushing syndrome over five months without an identifiable source of EAS, the decision was made to proceed with bilateral adrenalectomy and perform surveillance imaging to identify growth of a possible occult NET. Conclusion: In our case, DOTATATE-PET did not help to localize an ACTH-secreting NET, suggesting that the sensitivity of this study might not be as good as reported for other types of NET. Therefore, Occult EAS remains a diagnostic challenge and clinicians may resort to bilateral adrenalectomy for permanent biochemical control and serial CT imaging to detect an incipient NET.

Background: Distant metastasis from Squamous Cell Carcinoma (SCC) of the Vulva is very rare and typically associated with poor outcomes. In the literature, there have been no reported cases of vulvar SCC with metastasis to the thyroid, which augments the uniqueness of the case we are presenting. Clinical Case: A 29-year-old female was hospitalized for abdominal pain & altered mental status. Labs showed calcium 21 (RR 8.5-10.5 mg/dL) with iPTH 4.3 (RR 12-88 pg/mL). Imaging revealed an 8.6 x 7.2 cm right thyroid mass (solid with cystic internal components, hyperechoic to isoechoic, wider than tall, lobulated margins, punctate echogenic foci occupying nearly the entire right lobe, minimal vascularity), mildly effacing the trachea. There were also extensive lesions consistent with systemic metastasis involving the left hilar lymph nodes, pre-tracheal lymph nodes, right hepatic lobe, head of pancreas, retroperitoneal lymph nodes, right inferior pubic ramus, proximal right humerus, left humerus, proximal femur & frontal lobe of the brain. Hypercalcemia of malignancy from an unknown cancer was diagnosed. FNA biopsy of the thyroid mass was consistent with atypia of undetermined significance. Liver biopsy showed evidence of high grade carcinoma with non-calcitonin producing neuroendocrine differentiation. Labs showed serum serotonin 11 (RR 56-244 ng/mL), CA 19-9 &lt; 0.8 (RR 0-35 U/mL), alpha-fetoprotein 2.12 (RR 0-9 ng/mL), CEA 20.97 (RR 0-2.9 ng/mL), PTHrP 33 (RR 14-27 pg/mL), 1,25OH Vit D 18 (RR 18-72 pg/mL), chromogranin A 189 (RR 25-140 pg/mL), & calcitonin &lt; 2 (RR &lt; 5 pg/mL). A vaginal lesion was discovered on exam & biopsy showed squamous cells with cytopathic effect of Herpes Simplex Virus (confirmed with immunohistochemical stain). Subsequent biopsy of the brain & core needle biopsy of the thyroid showed morphology similar to a concurrent biopsy of a vulvar lesion also found on exam: poorly differentiated SCC. The patient was diagnosed with vulvar SCC with extensive metastasis. Her hospital course was complicated by atrial fibrillation, acute respiratory failure, & sepsis. She, unfortunately, passed away from her severe morbidities. Discussion: Metastasis to the thyroid is an infrequent occurrence. It is commonly encountered in breast, lung & renal cell carcinomas. It can occur due to direct spread from adjacent tissues or by lymphatic or hematogenous spread. Thyroid gland metastasis is more commonly seen in patients with aggressive or widespread carcinomas, especially by hematogenous route, due to the thyroid’s extensive vascularity. Conclusion: Thyroid gland metastasis, particularly due to vulvar SCC, is a rare entity with a poor prognosis. In patients with extensive poorly differentiated carcinoma such as our patient, it is of utmost importance to identify suspicious thyroid nodules and perform comprehensive diagnostic testing to facilitate timely intervention for improved outcomes.

Background Hypercholesterolemia (HC) in cholestatic liver disease commonly involves a high lipoprotein-X (LpX) and low LDL receptors. No evidence has been found to suggest the association of LpX with an increased risk of cardiovascular disease (CVD). Hence, lipid lowering therapy is unnecessary as HC improves with treatment of cholestasis, but plasmapheresis should be considered in markedly elevated LDL values given the uncertainty of short term complications. Clinical Case A 47-year-old man with HTN, DMT2, nephrotic syndrome secondary to DM glomerulosclerosis and CKD stage 3 was admitted for an NSTEMI and acute heart failure due to non-ischemic cardiomyopathy. On exam he had jaundice and hepatomegaly without xanthelasma or tendon xanthomas. Laboratory evaluation revealed elevated HDL 200 [35-75 mg/dl], LDL 2,182 [0-130 mg/dl] and triglyceride 326 [30-150 mg/dl] although his lipid panel four months ago was normal. He had no family history of HC or premature CAD. Interestingly, two months prior the patient was seen in GI clinic due to jaundice, pruritus, acholia and coluria. Work-up showed cholestasis with total bilirubin 5.2 [0.1-1.2 mg/dl], AST 148 [0-40 U/L], ALT 112 [5-25 U/L], alkaline phosphatase 1,874 [20-120 U/L] and GGT 2,307 [3-60 U/L]. Further evaluation was unrevealing with negative viral hepatitis serologies, antinuclear antibodies, anti-smooth muscle antibody, anti-mitochondrial antibody, ceruloplasmin, α-1antitrypsin. He underwent liver biopsy which demonstrated cholestatic hepatitis with advanced biliary fibrosis, lymphocytic cholangitis and perivenular infiltrate thought secondary to an atypical autoimmune cholangiopathy. Due to concern for hyperviscosity and potential CVD complications, two sessions of plasma exchange were performed with a rapid lowering of LDL to 661 mg/dL. He was given a dose of evolocumab and discharged on ursodeoxycholic acid with improvement in liver function and normalization of lipid panel within three weeks. His HC was presumed mainly from atypical autoimmune cholangiopathy. LpX was unlikely since his Apolipoprotein B was elevated at 239 [RR 52-109 mg/dl]. Once his liver function normalized, he was started on high intensity statin and ezetimibe due to an elevated CVD risk with a low ApoA 30 mg/dL [RR 94-176]. Conclusion This is a rare case of cholestatic liver disease causing markedly elevated LDL, successfully managed with plasma exchange and ursodeoxycholic acid with subsequent resolution of LDL abnormality. References 1. Cohen LB, Ambinder EP, Wolke AM, Field SP, Schaffner F. Role of plasmapheresis in primary biliary cirrhosis. Gut. 1985;26(3):291-4. 2. Suraweera D, Fanous C, Jimenez M, Tong MJ, Saab S. Risk of Cardiovascular Events in Patients with Primary Biliary Cholangitis - Systematic Review. J Clin Transl Hepatol. 2018;6(2):119-126.