Transcript Ectopic_Hormone_Syndromes

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 9th 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

Non-islet Cell tumor

Usually bulky mesenchymal tumors
–
–
–
–
–
Fibrosarcomas
Rhabdomyosarcomas
Leiomyosarcomas
Mesotheliomas
hemangiopericytomas
Make up 50%
Hepatomas, carcinoid tumors, and
adrenocortical carcinomas account for
25%
 See suppressed insulin, GH, and IGF
binding proteins

Why hypoglycemia?
Tumors secrete increased amounts of IGFII
 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
I131 scan of
neck
I131 scan of
pelvis
Pelvic CT
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
