Thyroid hormone induced brown adipose tissue and amelioration of diabetes in a patient with extreme insulin resistance.
BACKGROUND
Brown adipose tissue (BAT) found by positron emission/computed tomography (PET-CT) using flouro-deoxyglucose (FDG) is inducible by cold exposure in men. Factors leading to increased BAT are of great interest for its potential role in the treatment of diabetes and obesity.


OBJECTIVE
We tested whether thyroid hormone (TH) levels are related to the volume and activity of BAT in a patient with a mutation in the insulin receptor gene. DESIGN/SETTING/INTERVENTION: Our work was based on the case report of a patient in an observational study at the National Institutes of Health.


METHODS
The patient discontinued insulin and oral antidiabetics after thyroidectomy and suppressive-dose levothyroxine therapy for thyroid cancer. PET-CT uptake in BAT was confirmed by histology and molecular analysis.


RESULTS
PET-CT studies were performed, and we measured hemoglobin A1c and resting energy expenditure before and after levothyroxine discontinuation for thyroid cancer testing. Molecular studies of BAT and white adipose samples are presented.


RESULTS
Supraclavicular and periumbilical sc adipose tissue demonstrated molecular features of BAT including uncoupling protein-1, type 2 deiodinase, and PR domain containing 16 by quantitative PCR. Activity of type 2 deiodinase activity was increased. The discontinuation of levothyroxine resulted in decreased FDG uptake and diminished volume of BAT depots accompanied by worsening of diabetic control.


CONCLUSIONS
This case demonstrates the TH effect on BAT activity and volume in this patient and an association between BAT activity and glucose levels in this patient. Because the contribution of TH on skeletal muscle energy expenditure and fuel metabolism was not assessed, an association between BAT activity and glucose homeostasis can only be suggested.
Skarulis
Monica C
MC
Clinical Endocrine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892-1613, USA. monica_skarulis@nih.gov
Celi
Francesco S
FS
Mueller
Elisabetta
E
Zemskova
Marina
M
Malek
Rana
R
Hugendubler
Lynne
L
Cochran
Craig
C
Solomon
Jeffrey
J
Chen
Clara
C
Gorden
Phillip
P
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000473:pathology*; D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects; D003920:Diabetes Mellitus / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D009929:Organ Size; D011972:Receptor, Insulin / Q000235:genetics; D013963:Thyroid Hormones / Q000097:blood / Q000494:pharmacology / Q000502:physiology*
D013963:Thyroid Hormones; D011972:Receptor, Insulin