Ectopic Hormone Ectopic Hormone SyndromesSyndromes

Case 1Case 1

65 y/o F presents with 20 lb weight 65 y/o F presents with 20 lb weight loss over last 2 months, new onset loss over last 2 months, new onset hyperglycemia, HTN, and hyperglycemia, HTN, and hypokalemiahypokalemia

Pt is markedly hyperpigmented and Pt is markedly hyperpigmented and cachecticcachectic

Chest X-rayChest X-ray

Ectopic Cushing’s SyndromeEctopic Cushing’s Syndrome

Due to production of ACTH, or rarely CRH, Due to production of ACTH, or rarely CRH, from source other than from source other than pituitary/hypothalamuspituitary/hypothalamus

15% of all Cushing’s Syndrome15% of all Cushing’s Syndrome Tumors can be very aggressive and Tumors can be very aggressive and

therefore pt’s present more like cancer therefore pt’s present more like cancer than Cushing’s, or can be indolent tumors than Cushing’s, or can be indolent tumors and present like Cushing’sand present like Cushing’s

Tumors express POMC which is then Tumors express POMC which is then processed to ACTH and MSHprocessed to ACTH and MSH

Ectopic Cushing’sEctopic Cushing’s

Make diagnosis by documenting Make diagnosis by documenting elevated cortisol levels:elevated cortisol levels:– 24 urine free cortisol24 urine free cortisol– Low dose and high dose dex Low dose and high dose dex

suppressionsuppression– Inferior Petrosal Sinus SamplingInferior Petrosal Sinus Sampling

Can be hard to detectCan be hard to detect– Chest/Abd/Pelvis imagingChest/Abd/Pelvis imaging– Octreotide scansOctreotide scans

TreatmentTreatment

If find tumor, surgically resectIf find tumor, surgically resect If can’t find tumor or if tumor If can’t find tumor or if tumor

unresectable, can treat medicallyunresectable, can treat medically– KetoconazoleKetoconazole– MetyraponeMetyrapone– KetamineKetamine– AminoglutethamideAminoglutethamide– MitotaneMitotane

Case 2Case 2

68 y/o M presents w/ dehydration 68 y/o M presents w/ dehydration and mental status changesand mental status changes

Labs show Ca=16.5 mg/ dLLabs show Ca=16.5 mg/ dL

PTH Related ProteinPTH Related Protein

A protein expressed in many cells whose A protein expressed in many cells whose main function is growth and differentiationmain function is growth and differentiation

Occupies PTH receptor to carry out it’s Occupies PTH receptor to carry out it’s functionsfunctions

However, when make large amounts of it, However, when make large amounts of it, acts like PTH to:acts like PTH to:– Increase osteoclast functionIncrease osteoclast function– Increase conversion of 25 to 1,25 vitamin D Increase conversion of 25 to 1,25 vitamin D

leading to increased absorption of calcium leading to increased absorption of calcium through the gutthrough the gut

– Increase renal resorption of calciumIncrease renal resorption of calcium

Tumors that make PTH-rpTumors that make PTH-rp

Renal CellRenal Cell Squamous cellSquamous cell BladderBladder MelanomaMelanoma Breast Breast ProstateProstate

TreatmentTreatment

HydrationHydration IV BisphosphonatesIV Bisphosphonates Subq calcitoninSubq calcitonin Treat underlying malignancyTreat underlying malignancy

Case 3Case 3

A 25 y/o M presents with multiple A 25 y/o M presents with multiple stress fractures, bone pain, and stress fractures, bone pain, and muscle weaknessmuscle weakness

He had a tender mass at the right He had a tender mass at the right posterior 9posterior 9thth rib rib

Labs show Phosphate=0.8 mmol/dLLabs show Phosphate=0.8 mmol/dL Normal calciumNormal calcium Elevated alk phosElevated alk phos

CXRCXR

Bone ScanBone Scan

Oncogenic OsteomalaciaOncogenic Osteomalacia

Also called Tumor Induced OsteomalaciaAlso called Tumor Induced Osteomalacia See renal phosphate wasting and vitamin See renal phosphate wasting and vitamin

D abnormalitiesD abnormalities Get inappropriate phosphate renal wasting Get inappropriate phosphate renal wasting

due to excess production of fibroblast due to excess production of fibroblast growth factors (phosphotonins), most growth factors (phosphotonins), most common is FGF 23common is FGF 23

FGFs inhibit phosphate reabsorption at the FGFs inhibit phosphate reabsorption at the proximal tubule, and also inhibit 1proximal tubule, and also inhibit 1 hydroxylation of 25 vit Dhydroxylation of 25 vit D

Oncogenic OsteomalaciaOncogenic Osteomalacia

Tumors are usually benign and derived Tumors are usually benign and derived from bone or soft tissuefrom bone or soft tissue

Can be very hard to find—look in mouth, Can be very hard to find—look in mouth, sinuses, and extremitiessinuses, and extremities

Some reports that PET and octreotide Some reports that PET and octreotide scanning were able to localize the tumorscanning were able to localize the tumor

Treatment is resection of tumor, but if Treatment is resection of tumor, but if can’t find treat w/ phosphate replacement can’t find treat w/ phosphate replacement and calcitrioland calcitriol

Oncogenic OsteomalaciaOncogenic Osteomalacia

Case 4Case 4

65 y/o M presents 65 y/o M presents with hypoglycemia. with hypoglycemia. No hx of DM and no No hx of DM and no access to DM meds. access to DM meds.

CT scan looking for CT scan looking for pancreatic mass pancreatic mass finds a large finds a large retroperitoneal massretroperitoneal mass

Insulin levels are low Insulin levels are low

Non-islet Cell tumor Non-islet Cell tumor

Usually bulky mesenchymal tumorsUsually bulky mesenchymal tumors– FibrosarcomasFibrosarcomas– RhabdomyosarcomasRhabdomyosarcomas– LeiomyosarcomasLeiomyosarcomas– MesotheliomasMesotheliomas– hemangiopericytomas hemangiopericytomas

Hepatomas, carcinoid tumors, and Hepatomas, carcinoid tumors, and adrenocortical carcinomas account for adrenocortical carcinomas account for 25%25%

See suppressed insulin, GH, and IGF See suppressed insulin, GH, and IGF binding proteinsbinding proteins

Make up 50%

Why hypoglycemia?Why hypoglycemia?

Tumors secrete increased amounts of IGF-Tumors secrete increased amounts of IGF-IIII

There is altered binding increasing it’s There is altered binding increasing it’s bioavailability and effectbioavailability and effect

More IGF-II goes to insulin receptors in More IGF-II goes to insulin receptors in tissues leading to:tissues leading to:– Increased clearance of glucose from circulation Increased clearance of glucose from circulation

to muscleto muscle– Decreased hepatic gluconeogenesisDecreased hepatic gluconeogenesis– Suppression of lipolysisSuppression of lipolysis

TreatmentTreatment

Treat underlying malignancyTreat underlying malignancy GH, glucagon, glucocorticoids, or GH, glucagon, glucocorticoids, or

somatostatin have been effective in somatostatin have been effective in individual patients with unresectable individual patients with unresectable tumorstumors

Case 5Case 5

An 81 y/o F presents w/ tachycardia, An 81 y/o F presents w/ tachycardia, weight loss, tremors, and sweats.weight loss, tremors, and sweats.

TSH<0.01TSH<0.01 FT4=5.2FT4=5.2 Neck exam is unremarkableNeck exam is unremarkable Denies use of thyroid hormoneDenies use of thyroid hormone

ImagingImaging

Pelvic CT

I131 scan of neck

I131 scan of pelvis

Struma OvariiStruma Ovarii

An ovarian tumor containing thyroid tissue An ovarian tumor containing thyroid tissue as the predominant cell typeas the predominant cell type

Typically occur as part of a teratoma but Typically occur as part of a teratoma but may occasionally be encountered with may occasionally be encountered with serous or mucinous cystadenomasserous or mucinous cystadenomas

Malignant transformation is rareMalignant transformation is rare Most strumal tissue is not functionally Most strumal tissue is not functionally

active, and cases associated with active, and cases associated with thyrotoxicosis can be due to autoimmune thyrotoxicosis can be due to autoimmune stimulation of the normal thyroid glandstimulation of the normal thyroid gland

Struma OvariiStruma Ovarii

Between 0.8-3% of teratomas contain Between 0.8-3% of teratomas contain functional thyroid tissue or thyroid tissue functional thyroid tissue or thyroid tissue occupying most of the mass. They are thus occupying most of the mass. They are thus classified as a struma ovarii. classified as a struma ovarii. Approximately 15% of teratomas have a Approximately 15% of teratomas have a small, nonsignificant focus of thyroid small, nonsignificant focus of thyroid tissue.tissue.

The fifth and sixth decades are the ages of The fifth and sixth decades are the ages of peak frequencypeak frequency

Struma ovarii rarely occurs before pubertyStruma ovarii rarely occurs before puberty

Case 6Case 6

A 25 y/o M presents with A 25 y/o M presents with gynecomastia and symptoms of gynecomastia and symptoms of hyperthyroidismhyperthyroidism

Has slight goiter on examHas slight goiter on exam TSH<0.01, FT4-1.7TSH<0.01, FT4-1.7

Testicular UltrasoundTesticular Ultrasound

Germ Cell TumorGerm Cell Tumor

Can secrete HCG which leads to excess Can secrete HCG which leads to excess production of testosterone and estrogenproduction of testosterone and estrogen

Can also directly occupy TSH receptors Can also directly occupy TSH receptors causing hyperthyroidism similar to causing hyperthyroidism similar to pregnancypregnancy

Important to measure HCG in all men w/ Important to measure HCG in all men w/ gynecomastiagynecomastia

Can also be secreted from hepatic, biliary, Can also be secreted from hepatic, biliary, gastric, bladder, reanal, and pancreatic, gastric, bladder, reanal, and pancreatic, but often not bioligically activebut often not bioligically active