title: Effects of therapy with [177Lu-DOTA 0,Tyr 3]octreotate on endocrine function.
abstract: OBJECTIVE
  Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues is a novel therapy for patients with somatostatin receptor-positive tumours. We determined the effects of PRRT with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate) on glucose homeostasis and the pituitary-gonadal, pituitary-thyroid and pituitary-adrenal axes.
  
  
  METHODS
  Hormone levels were measured and adrenal function assessed at baseline and up to 24 months of follow-up.
  
  
  RESULTS
  In 35 men, mean serum inhibin B levels were decreased at 3 months post-therapy (205 +/- 16 to 25 +/- 4 ng/l, p < 0.05) and follicle-stimulating hormone (FSH) levels increased (5.9 +/- 0.5 to 22.7 +/- 1.4 IU/l, p < 0.05). These levels returned to near baseline levels. Total testosterone and sex hormone binding globulin (SHBG) levels decreased (15.0 +/- 0.9 to 10.6 +/- 1.0 nmol/l, p < 0.05 and 61.8 +/- 8.7 to 33.2 +/- 3.7 nmol, p < 0.05), respectively, whereas non-SHBG-bound T did not change. An increase (5.2 +/- 0.6 to 7.7 +/- 0.7 IU/l, p < 0.05) of luteinizing hormone (LH) levels was found at 3 months of follow-up returning to baseline levels thereafter. In 21 postmenopausal women, a decrease in levels of FSH (74.4 +/- 5.6 to 62.4 +/- 7.7 IU/l, p < 0.05) and LH (26.8 +/- 2.1 to 21.1 +/- 3.0 IU/l, p < 0.05) was found. Of 66 patients, 2 developed persistent primary hypothyroidism. Free thyroxine (FT(4)) levels decreased (17.7 +/- 0.4 to 15.6 +/- 0.6 pmol/l, p < 0.05), whereas thyroid-stimulating hormone (TSH) and triiodothyronine (T(3)) levels did not change. Reverse triiodothyronine (rT(3)) levels decreased (0.38 +/- 0.03 to 0.30 +/- 0.01 nmol/l, p < 0.05). Before and after therapy adrenocorticotropic hormone (ACTH) stimulation tests showed an adequate response of serum cortisol (> 550 nmol/l, n = 18). Five patients developed elevated HbA(1c) levels (> 6.5%).
  
  
  CONCLUSIONS
  In men (177)Lu-octreotate therapy induced transient inhibitory effects on spermatogenesis, but non-SHBG-bound T levels remained unaffected. In the long term, gonadotropin levels decreased significantly in postmenopausal women. Only a few patients developed hypothyroidism or elevated levels of HbA(1c). Therefore, PRRT with (177)Lu-octreotate can be regarded as a safe treatment modality with respect to short- and long-term endocrine function.
authors.affiliation: Department of Nuclear Medicine, Erasmus Medical Center, 3015 CE Rotterdam, The Netherlands. j.teunissen@erasmusmc.nl
authors.forename: Jaap J M
authors.initials: JJ
authors.lastname: Teunissen
authors.forename: Eric P
authors.initials: EP
authors.lastname: Krenning
authors.forename: Frank H
authors.initials: FH
authors.lastname: de Jong
authors.forename: Yolanda B
authors.initials: YB
authors.lastname: de Rijke
authors.forename: Richard A
authors.initials: RA
authors.lastname: Feelders
authors.forename: Maarten O
authors.initials: MO
authors.lastname: van Aken
authors.forename: Wouter W
authors.initials: WW
authors.lastname: de Herder
authors.forename: Dik J
authors.initials: DJ
authors.lastname: Kwekkeboom
mesh_terms: D000328:Adult; D000368:Aged; D004702:Endocrine Glands / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000528:radiation effects; D006728:Hormones / Q000097:blood; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000378:metabolism / Q000503:physiopathology / Q000532:radiotherapy; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000009:adverse effects* / Q000627:therapeutic use; D018000:Receptors, Peptide / Q000627:therapeutic use; D012189:Retrospective Studies; D013004:Somatostatin / Q000737:chemistry / Q000627:therapeutic use; D013997:Time Factors; D055815:Young Adult
chemical_list: D006728:Hormones; D009942:Organometallic Compounds; D018000:Receptors, Peptide; D013004:Somatostatin; C447941:lutetium Lu 177 dotatate; D005947:Glucose; D015282:Octreotide