Ectopic Hormone Syndromes

Case 1  65 y/o F presents with 20 lb weight loss over last 2 months, new onset hyperglycemia, HTN, and hypokalemia  Pt is markedly hyperpigmented and cachectic

Chest X-ray

Ectopic Cushing’s Syndrome  Due to production of ACTH, or rarely CRH, from source other than pituitary/hypothalamus  15% of all Cushing’s Syndrome  Tumors can be very aggressive and therefore pt’s present more like cancer than Cushing’s, or can be indolent tumors and present like Cushing’s  Tumors express POMC which is then processed to ACTH and MSH

Ectopic Cushing’s  Make diagnosis by documenting elevated cortisol levels: –24 urine free cortisol –Low dose and high dose dex suppression –Inferior Petrosal Sinus Sampling  Can be hard to detect –Chest/Abd/Pelvis imaging –Octreotide scans

Treatment  If find tumor, surgically resect  If can’t find tumor or if tumor unresectable, can treat medically –Ketoconazole –Metyrapone –Ketamine –Aminoglutethamide –Mitotane

Case 2  68 y/o M presents w/ dehydration and mental status changes  Labs show Ca=16.5 mg/ dL

PTH Related Protein  A protein expressed in many cells whose main function is growth and differentiation  Occupies PTH receptor to carry out it’s functions  However, when make large amounts of it, acts like PTH to: –Increase osteoclast function –Increase conversion of 25 to 1,25 vitamin D leading to increased absorption of calcium through the gut –Increase renal resorption of calcium

Tumors that make PTH-rp  Renal Cell  Squamous cell  Bladder  Melanoma  Breast  Prostate

Treatment  Hydration  IV Bisphosphonates  Subq calcitonin  Treat underlying malignancy

Case 3  A 25 y/o M presents with multiple stress fractures, bone pain, and muscle weakness  He had a tender mass at the right posterior 9 th rib  Labs show Phosphate=0.8 mmol/dL  Normal calcium  Elevated alk phos

CXR

Bone Scan

Oncogenic Osteomalacia  Also called Tumor Induced Osteomalacia  See renal phosphate wasting and vitamin D abnormalities  Get inappropriate phosphate renal wasting due to excess production of fibroblast growth factors (phosphotonins), most common is FGF 23  FGFs inhibit phosphate reabsorption at the proximal tubule, and also inhibit 1 hydroxylation of 25 vit D

Oncogenic Osteomalacia  Tumors are usually benign and derived from bone or soft tissue  Can be very hard to find—look in mouth, sinuses, and extremities  Some reports that PET and octreotide scanning were able to localize the tumor  Treatment is resection of tumor, but if can’t find treat w/ phosphate replacement and calcitriol

Oncogenic Osteomalacia

Case 4  65 y/o M presents with hypoglycemia. No hx of DM and no access to DM meds.  CT scan looking for pancreatic mass finds a large retroperitoneal mass  Insulin levels are low

Non-islet Cell tumor  Usually bulky mesenchymal tumors –Fibrosarcomas –Rhabdomyosarcomas –Leiomyosarcomas –Mesotheliomas –hemangiopericytomas  Hepatomas, carcinoid tumors, and adrenocortical carcinomas account for 25%  See suppressed insulin, GH, and IGF binding proteins Make up 50%

Why hypoglycemia?  Tumors secrete increased amounts of IGF- II  There is altered binding increasing it’s bioavailability and effect  More IGF-II goes to insulin receptors in tissues leading to: –Increased clearance of glucose from circulation to muscle –Decreased hepatic gluconeogenesis –Suppression of lipolysis

Treatment  Treat underlying malignancy  GH, glucagon, glucocorticoids, or somatostatin have been effective in individual patients with unresectable tumors

Case 5  An 81 y/o F presents w/ tachycardia, weight loss, tremors, and sweats.  TSH<0.01  FT4=5.2  Neck exam is unremarkable  Denies use of thyroid hormone

Imaging Pelvic CT I131 scan of neck I131 scan of pelvis

Struma Ovarii  An ovarian tumor containing thyroid tissue as the predominant cell type  Typically occur as part of a teratoma but may occasionally be encountered with serous or mucinous cystadenomas  Malignant transformation is rare  Most strumal tissue is not functionally active, and cases associated with thyrotoxicosis can be due to autoimmune stimulation of the normal thyroid gland

Struma Ovarii  Between 0.8-3% of teratomas contain functional thyroid tissue or thyroid tissue occupying most of the mass. They are thus classified as a struma ovarii. Approximately 15% of teratomas have a small, nonsignificant focus of thyroid tissue.  The fifth and sixth decades are the ages of peak frequency  Struma ovarii rarely occurs before puberty

Case 6  A 25 y/o M presents with gynecomastia and symptoms of hyperthyroidism  Has slight goiter on exam  TSH<0.01, FT4-1.7

Testicular Ultrasound

Germ Cell Tumor  Can secrete HCG which leads to excess production of testosterone and estrogen  Can also directly occupy TSH receptors causing hyperthyroidism similar to pregnancy  Important to measure HCG in all men w/ gynecomastia  Can also be secreted from hepatic, biliary, gastric, bladder, reanal, and pancreatic, but often not bioligically active