Amphetamine-Like Analogues in Diabetes: Speeding towards Ketogenesis

Obesity is common in patients with type 1 and type 2 diabetes. Amphetamine-like analogues comprise the most popular class of weight loss medications. We present a case of a 34-year-old African American female with a history of type 1 diabetes, dyslipidemia, and obesity who developed diabetic ketoacidosis (DKA) after starting Diethylpropion for the purpose of weight loss. Shortly after starting Diethylpropion, she developed nausea, vomiting, and periumbilical pain. Blood work revealed glucose of 718 mg/dL, pH 7.32 (7.35–7.45), bicarbonate 16 mmol/L (22–29 mmol/L), and anion gap 19 mmol/L (8–16 mmol/L). Urine analysis demonstrated large amount of ketones. She was hospitalized and successfully treated for DKA. Diethylpropion was discontinued. Amphetamine-like analogues administration leads to norepinephrine release from the lateral hypothalamus which results in the appetite suppression. Peripheral norepinephrine concentration rises as well. Norepinephrine stimulates adipocyte lipolysis and thereby increases nonesterified fatty acids (NEFA) availability. It promotes β-oxidation of NEFA to ketone bodies while decreasing metabolic clearance rate of ketones. In the setting of acute insulin deficiency these effects are augmented. Females are more sensitive to norepinephrine effects compared to males. In conclusion, amphetamine-like analogues lead to a release of norepinephrine which can result in a clinically significant ketosis, especially in the setting of insulin deficiency

Dual Paraneoplastic Endocrine Syndromes Heralding Onset of Extrapulmonary Small Cell Carcinoma: A Case Report and Narrative Review

ObjectiveExtrapulmonary small cell carcinoma (EPSCC) is rare and frequent metastases at presentation can complicate efforts to identify a site of origin. In particular, SCC comprises <1% of prostate cancers and has been implicated in castration resistance.MethodsClinical, laboratory, imaging, and pathology data are presented.ResultsA 56-year-old man with locally advanced prostate adenocarcinoma on androgen deprivation therapy presented with a clogged nephrostomy tube. Laboratory results included calcium 13.8 mg/dL (8.5–10.5 mg/dL), albumin 3.6 g/dL (3.5–5 mg/dL), and potassium 2.8 mmol/L (3.5–5.2 mmol/L). Hypercalcemia investigation revealed intact PTH 19 pg/mL (16–87 pg/mL), 25-OH vitamin D 15.7 ng/mL (>30 ng/mL), and PTH-related peptide (PTHrP) 63.4 pmol/L (<2.3 pmol/L). Workup for hypokalemia yielded aldosterone 5.3 ng/dL (<31 ng/dL), renin 0.6 ng/mL/h (0.5–4 ng/mL/h), and 6:00 a.m. cortisol 82 µg/dL (6.7–22.6 µg/dL) with ACTH 147 pg/mL (no ref. range). High-dose Dexamethasone suppression testing suggested ACTH-dependent ectopic hypercortisolism. Contrast-enhanced CT findings included masses in the liver and right renal pelvis, a heterogeneous enlarged mass in the region of the prostate invading the bladder, bilateral adrenal thickening, and lytic lesions in the pelvis and spine. Liver biopsy identified epithelioid malignancy with Ki proliferation index 98% and immunohistochemical staining positive for synaptophysin and neuron-specific enolase, compatible with high-grade small cell carcinoma. Staining for ACTH was negative; no stain for CRH was available. Two weeks after chemotherapy, 6:00 a.m. cortisol normalized and CT scans showed universal improvement.ConclusionExtensive literature details paraneoplastic syndromes associated with SCC, but we report the first case of EPSCC diagnosed due to onset of dual paraneoplastic syndromes