Hemoglobin decline as a signal for hyperprolactinemia onset prior to prolactinoma diagnosis in hypogonadal men.
anemia
hemoglobin
male
prolactin
prolactinoma
Journal
Andrology
ISSN: 2047-2927
Titre abrégé: Andrology
Pays: England
ID NLM: 101585129
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
revised:
14
02
2023
received:
25
12
2022
accepted:
04
03
2023
medline:
25
9
2023
pubmed:
11
3
2023
entrez:
10
3
2023
Statut:
ppublish
Résumé
Men harboring prolactinomas frequently suffer from central hypogonadism with secondary anemia. They present insidious and nonspecific symptoms of hypogonadism, making it difficult to diagnose the disease and determine its duration. The result is a delay in diagnosis, which may have harmful hormonal and metabolic consequences. We hypothesized that a decrease in hemoglobin (HB) levels prior to prolactinoma diagnosis, may signal hyperprolactinemia onset and estimate disease duration. We retrospectively evaluated the prediagnosis temporal trends in HB levels of 70 males with prolactinoma, diagnosed from January 2010 to July 2022. Men without hypogonadism, patients that received testosterone, and those with unrelated anemia were excluded. Sixty-one of seventy men (87%) with prolactinoma presented with hypogonadism, and forty men (57%) had HB levels ≤13.5 g/dL at diagnosis. We identified 25 patients with "informative" HB curves (mean age, 46.1±14.9 years; median prolactin, 952 ng/mL; median follow-up, 14.0 years), demonstrating an obvious prediagnosis HB decrease (greater than 1.0 g/dL), from a prediagnosis baseline HB of 14.4 ± 0.3 to 12.9 ± 0.5 g/dL at diagnosis. The median "low-HB duration" (from the first low HB measurement to hyperprolactinemia diagnosis) was 6.1 years (IQR, 3.3-8.8 years). In symptomatic patients, we identified a correlation between "low-HB duration" and patient-reported sexual dysfunction duration (n = 17, R = 0.502, p = 0.04). The "low-HB duration" was significantly longer than the reported sexual dysfunction duration (7.0 ± 4.5 vs. 2.9 ± 2.5 years, p = 0.01). In our cohort of men with prolactinomas and hypogonadism, we found a marked decrease in HB levels that preceded prolactinoma diagnosis by a median of 6.1 years, with a mean delay of 4.1 years between HB decrease and hypogonadal symptoms appearance. These results suggest that HB decline prior to prolactinoma diagnosis may serve as a marker for hyperprolactinemia onset in a subset of hypogonadal men and allow a more accurate assessment of disease duration.
Sections du résumé
BACKGROUND
Men harboring prolactinomas frequently suffer from central hypogonadism with secondary anemia. They present insidious and nonspecific symptoms of hypogonadism, making it difficult to diagnose the disease and determine its duration. The result is a delay in diagnosis, which may have harmful hormonal and metabolic consequences. We hypothesized that a decrease in hemoglobin (HB) levels prior to prolactinoma diagnosis, may signal hyperprolactinemia onset and estimate disease duration.
METHODS
We retrospectively evaluated the prediagnosis temporal trends in HB levels of 70 males with prolactinoma, diagnosed from January 2010 to July 2022. Men without hypogonadism, patients that received testosterone, and those with unrelated anemia were excluded.
RESULTS
Sixty-one of seventy men (87%) with prolactinoma presented with hypogonadism, and forty men (57%) had HB levels ≤13.5 g/dL at diagnosis. We identified 25 patients with "informative" HB curves (mean age, 46.1±14.9 years; median prolactin, 952 ng/mL; median follow-up, 14.0 years), demonstrating an obvious prediagnosis HB decrease (greater than 1.0 g/dL), from a prediagnosis baseline HB of 14.4 ± 0.3 to 12.9 ± 0.5 g/dL at diagnosis. The median "low-HB duration" (from the first low HB measurement to hyperprolactinemia diagnosis) was 6.1 years (IQR, 3.3-8.8 years). In symptomatic patients, we identified a correlation between "low-HB duration" and patient-reported sexual dysfunction duration (n = 17, R = 0.502, p = 0.04). The "low-HB duration" was significantly longer than the reported sexual dysfunction duration (7.0 ± 4.5 vs. 2.9 ± 2.5 years, p = 0.01).
CONCLUSIONS
In our cohort of men with prolactinomas and hypogonadism, we found a marked decrease in HB levels that preceded prolactinoma diagnosis by a median of 6.1 years, with a mean delay of 4.1 years between HB decrease and hypogonadal symptoms appearance. These results suggest that HB decline prior to prolactinoma diagnosis may serve as a marker for hyperprolactinemia onset in a subset of hypogonadal men and allow a more accurate assessment of disease duration.
Substances chimiques
Prolactin
9002-62-4
Hemoglobins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1398-1407Informations de copyright
© 2023 American Society of Andrology and European Academy of Andrology.
Références
Duskin-Bitan H, Shimon I. Prolactinomas in males: any differences? Pituitary. 2020;23(1):52-57. doi:10.1007/s11102-019-01009-y
Delgrange E, Trouillas J, Maiter D, Donckier J, Tourniaire J. Sex-related difference in the growth of prolactinomas: a clinical and proliferation marker study. J Clin Endocrinol Metab. 1997;82(7):2102-2107. doi:10.1210/jcem.82.7.4088
Stoffel-Wagner B, Stöger P, Klingmüller D. Erstsymptome und anamnesezeiten bei 517 patienten mit hypophysenadenomen (Initial symptoms and anamnestic time in 517 patients with pituitary adenoma). Dtsch Med Wochenschr. 1997;122(8):213-219. doi:10.1055/s-2008-1047599
Berezin M, Shimon I, Hadani M. Prolactinoma in 53 men: clinical characteristics and modes of treatment (male prolactinoma). J Endocrinol Invest. 1995;18(6):436-441. doi:10.1007/BF03349742
Hulting AL, Muhr C, Lundberg PO, Werner S. Prolactinomas in men: clinical characteristics and the effect of bromocriptine treatment. Acta Med Scand. 1985;217(1):101-109. doi:10.1111/j.0954-6820.1985.tb01642.x
Brue T, Castinetti F. The risks of overlooking the diagnosis of secreting pituitary adenomas. Orphanet J Rare Dis. 2016;11(1):135. doi:10.1186/s13023-016-0516-x
Spark RF, Wills CA, O'Reilly G, Ransil BJ, Bergland R. Hyperprolactinaemia in males with and without pituitary macroadenomas. Lancet. 1982;2(8290):129-132. doi:10.1016/s0140-6736(82)91094-7
Fernandez A, Karavitaki N, Wass JA. Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol (Oxf). 2010;72(3):377-382. doi:10.1111/j.1365-2265.2009.03667.x
Mazziotti G, Porcelli T, Mormando M, et al. Vertebral fractures in males with prolactinoma. Endocrine. 2011;39(3):288-293. doi:10.1007/s12020-011-9462-5
Andereggen L, Frey J, Andres RH, et al. Persistent bone impairment despite long-term control of hyperprolactinemia and hypogonadism in men and women with prolactinomas. Sci Rep. 2021;11(1):5122. doi:10.1038/s41598-021-84606-x. Published 2021 Mar 4.
Hamidi O, Van Gompel J, Gruber L, et al. Management and outcomes of giant prolactinoma: a series of 71 patients. Endocr Pract. 2019;25(4):340-352. doi:10.4158/EP-2018-0392
Vestergaard P, Jørgensen JO, Hagen C, et al. Fracture risk is increased in patients with GH deficiency or untreated prolactinomas-a case-control study. Clin Endocrinol (Oxf). 2002;56(2):159-167. doi:10.1046/j.0300-0664.2001.01464.x
Ben-Jonathan N, LaPensee CR, LaPensee EW. What can we learn from rodents about prolactin in humans. Endocr Rev. 2008;29(1):1-41. doi:10.1210/er.2007-0017
Berinder K, Nyström T, Höybye C, Hall K, Hulting AL. Insulin sensitivity and lipid profile in prolactinoma patients before and after normalization of prolactin by dopamine agonist therapy. Pituitary. 2011;14(3):199-207. doi:10.1007/s11102-010-0277-9
Auriemma RS, Galdiero M, Vitale P, et al. Effect of chronic cabergoline treatment and testosterone replacement on metabolism in male patients with prolactinomas. Neuroendocrinology. 2015;101(1):66-81. doi:10.1159/000371851
Vahlquist B. The cause of the sexual differences in erythrocyte hemoglobin and serum iron levels in human adults. Blood. 1950;5(9):874-875.
Coviello AD, Kaplan B, Lakshman KM, Chen T, Singh AB, Bhasin S. Effects of graded doses of testosterone on erythropoiesis in healthy young and older men. J Clin Endocrinol Metab. 2008;93(3):914-919. doi:10.1210/jc.2007-1692
Ellegala DB, Alden TD, Couture DE, Vance ML, Maartens NF. Anemia, testosterone, and pituitary adenoma in men. J Neurosurg. 2003;98(5):974-977. doi:10.3171/jns.2003.98.5.0974
Shimon I, Benbassat C, Tzvetov G, Grozinsky-Glasberg S. Anemia in a cohort of men with macroprolactinomas: increase in hemoglobin levels follows prolactin suppression. Pituitary. 2011;14(1):11-15. doi:10.1007/s11102-010-0251-6
Iglesias P, Castro JC, Díez JJ. Clinical significance of anaemia associated with prolactin-secreting pituitary tumours in men. Int J Clin Pract. 2011;65(6):669-673. doi:10.1111/j.1742-1241.2011.02662.x
Karavitaki N, Thanabalasingham G, Shore HC, et al. Do the limits of serum prolactin in disconnection hyperprolactinaemia need re-definition? A study of 226 patients with histologically verified non-functioning pituitary macroadenoma. Clin Endocrinol (Oxf). 2006;65(4):524-529. doi:10.1111/j.1365-2265.2006.02627.x
Adeli K, Raizman JE, Chen Y, et al. Complex biological profile of hematologic markers across pediatric, adult, and geriatric ages: establishment of robust pediatric and adult reference intervals on the basis of the Canadian Health Measures Survey. Clin Chem. 2015;61(8):1075-1086. doi:10.1373/clinchem.2015.240531
Maclean FR, Hanley JP. Prolactinoma presenting as chronic anaemia with osteoporosis: a case report. J Med Case Rep. 2010;4:33. doi:10.1186/1752-1947-4-33
Iglesias P, Díez JJ. Chronic anemia as first clinical manifestation of a prolactin-secreting pituitary macroadenoma in a male patient. Am J Med. 2011;124(6):e3-e4. doi:10.1016/j.amjmed.2010.12.023
Greenspan SL, Neer RM, Ridgway EC, Klibanski A. Osteoporosis in men with hyperprolactinemic hypogonadism. Ann Intern Med. 1986;104(6):777-782. doi:10.7326/0003-4819-104-6-777
Greenman Y, Tordjman K, Stern N. Increased body weight associated with prolactin secreting pituitary adenomas: weight loss with normalization of prolactin levels. Clin Endocrinol (Oxf). 1998;48(5):547-553. doi:10.1046/j.1365-2265.1998.00403.x
Ausk KJ, Ioannou GN. Is obesity associated with anemia of chronic disease? A population-based study. Obesity (Silver Spring). 2008;16(10):2356-2361. doi:10.1038/oby.2008.353
Gauci R, Hunter M, Bruce DG, Davis WA, Davis TME. Anemia complicating type 2 diabetes: prevalence, risk factors and prognosis. J Diabetes Complications. 2017;31(7):1169-1174. doi:10.1016/j.jdiacomp.2017.04.002
Corona G, Goulis DG, Huhtaniemi I, et al. European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males: endorsing organization: European Society of Endocrinology. Andrology. 2020;8(5):970-987. doi:10.1111/andr.12770
Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore longitudinal study of aging. J Clin Endocrinol Metab. 2001;86(2):724-731. doi:10.1210/jcem.86.2.7219