Difficulties in diagnosis of adenomas with mixed prolactin and growth hormone secretion: case presentation

Hyperpolactinemia is a persistent excess of prolactin in the blood serum. The symptom complex of hyperprolactinemia primarily consists of disturbances in function of the reproductive system. The secretion of prolactin is under complex neuroendocrine control, which involves factors of different nature: neurotransmitters, hormones of the peripheral endocrine glands. In most cases, prolactin is secreted by pituitary cells - lactotrophs, but in some cases, hypersecretion of prolactin is combined with an excess production of growth hormone, which is typical for tumors originating from the line of progenitor cells of lactotrophs and somatotrophs of the pituitary gland, mammosomatotrophs. In this case, the symptom complex of hyperprolactinemia is accompanied by clinical manifestations of acromegaly. In patients with acromegaly, the cause of hyperprolactinemia may be pituitary stalk compression or mixed secretion of prolactin and growth hormone. Differentiation of lactotropic and somatotropic pituitary cells is determined by transcription factor Pit-1. These cell lineages are closely connected,  and this may be one of the reasons for formation of tumors with mixed secretion. Reports of late presentation of acromegaly in patients previously diagnosed with prolactinomas have also been described in literature.

Clinical manifestations of hyperprolactinemia can cause the patient to seek doctor’s attention before acromegalic changes in appearance develop. Careful attention is needed both to the primary diagnosis and to the clinical course of the disease in patients with hyperprolactinemia and pituitary adenoma: full assessment of hormonal status with mandatory evaluation of IGF-1 is crucial at initial examination, during further observation it may be advised to consider periodic evaluation of IGF-1 in addition to assessment of prolactin and the size of adenoma.  Pituitary adenomas with mixed secretion may have a poorer prognosis.

1. Lavrentaki A, Paluzzi A, Wass JAH, Karavitaki N. Epidemiology of acromegaly: review of population studies. Pituitary. 2017;20(1):4-9. doi: https://doi.org/10.1007/s11102-016-0754-x

2. Molitvoslovova NN. Acromegaly: recent progress in diagnostics and treatment. Problems of Endocrinology. 2011;57(1):46-59. (In Russ.). doi: https://doi.org/10.14341/probl201157146-59

3. Vilar L, Vilar CF, Lyra R, Lyra R, Naves LA. Acromegaly: clinical features at diagnosis. Pituitary. 2017;20(1):22-32. doi: https://doi.org/10.1007/s11102-016-0772-8

4. Pivonello R, Auriemma RS, Grasso LFS, et al. Complications of acromegaly: cardiovascular, respiratory and metabolic comorbidities. Pituitary. 2017;20(1):46-62. doi: https://doi.org/10.1007/s11102-017-0797-7

5. Grynberg M, Salenave S, Young J, Chanson P Female Gonadal Function before and after Treatment of Acromegaly. J Clin Endocrinol Metab. 2010;95(10):4518-4525. doi: https://doi.org/10.1210/jc.2009-2815

6. Lugo G, Pena L, Cordido F. Clinical Manifestations and Diagnosis of Acromegaly. Int J Endocrinol. 2012;2012(10):1-10. doi: https://doi.org/10.1155/2012/540398

7. Syro L V., Rotondo F, Serna CA, Ortiz LD, Kovacs K. Pathology of GH-producing pituitary adenomas and GH cell hyperplasia of the pituitary. Pituitary. 2017;20(1):84-92. doi: https://doi.org/10.1007/s11102-016-0748-8

8. Mitrofanova LB, Konovalov P V., Krylova JS, Polyakova VO, Kvetnoy IM. Plurihormonal cells of normal anterior pituitary: Facts and conclusions. Oncotarget. 2017;8(17):29282-29299. doi: https://doi.org/10.18632/oncotarget.16502

9. Osamura RY, Egashira N, Miyai S, et al. Molecular pathology of the pituitary. In: George Kontogeorgos, Kalman Kavacs, editors. Molecular Pathology of the Pituitary Front Horm Res. Basel, Karger. 2004;32:20-33.

10. Labadzhyan A, Melmed S. Plurihormonal Adenomas. In: Tritos N.A., Klibanski A., editors. Prolactin Disorders: From Basic Science to Clinical Management. Humana Press; 2019: 205-217.

11. Lania AG, Ferrero S, Pivonello R, et al. Evolution of an Aggressive Prolactinoma into a Growth Hormone Secreting Pituitary Tumor Coincident with GNAS Gene Mutation. J Clin Endocrinol Metab. 2010;95(1):13-17. doi: https://doi.org/10.1210/jc.2009-1360

12. Gadelha MR, Kasuki L, Korbonits M. The genetic background of acromegaly. Pituitary. 2017;20(1):10-21. doi: https://doi.org/10.1007/s11102-017-0789-7

13. Chanson P Maiter D. The epidemiology, diagnosis and treatment of Prolactinomas: The old and the new. Best Pract Res Clin Endocrinol Metab. 2019;33(2):101290. doi: https://doi.org/10.1016/jbeem.2019.101290

14. Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis and Treatment of Hyperprolactinemia: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011;96(2):273-288. doi: https://doi.org/10.1210/jc.2010-1692

15. Manuylova E, Calvi LM, Hastings C, et al. Late presentation of acromegaly in medically controlled prolactinoma patients. Endocrinol Diabetes Metab Case Reports. 2016;2016(2):273-288. doi: https://doi.org/10.1530/EDM-16-0069

16. Dessimoz C, Browaeys P Maeder P et al. Transformation of a Microprolactinoma into a Mixed Growth Hormone and Prolactin-Secreting Pituitary Adenoma. Front Endocrinol (Lausanne). 2012;2(2):273-288. doi: https://doi.org/10.3389/fendo.2011.00116

17. Andersen M, Hagen C, Frystyk J, Schroeder H, Hagen C. Development of acromegaly in patients with prolactinomas. Eur J Endocrinol. 2003;2(2):17-22. doi: https://doi.org/10.1530/eje.0.1490017

18. Rosario PW, Purisch S. Biochemical acromegaly in patients with prolactinoma during treatment with dopaminergic agonists. Arq Bras Endocrinol Metabol. 2010;54(6):546-549. doi: https://doi.org/10.1590/S0004-27302010000600006

19. Rick J, Jahangiri A, Flanigan PM, et al. Growth hormone and prolactin-staining tumors causing acromegaly: a retrospective review of clinical presentations and surgical outcomes. J Neurosurg. 2019;131(1):147-153. doi: https://doi.org/10.3171/2018.4JNS18230

20. Wang M, Mou C, Jiang M, et al. The characteristics of acromegalic patients with hyperprolactinemia and the differences in patients with merely GH-secreting adenomas: clinical analysis of 279 cases. Eur J Endocrinol. 2012;166(5):797-802. doi: https://doi.org/10.1530/EJE-11-1119

21. Huan C, Cui G, Ren Z. The characteristics of acromegalic patients with hyperprolactinemia and the differences with hyperprolactinemia patients. PakJPharmSci. 2015;28(2 Suppl):713-718.

22. Petersenn S, Giustina A. Diagnosis and management of prolactinomas: current challenges. Pituitary. 2020;23(1):1-2. doi: https://doi.org/10.1007/s11102-019-01025-y

23. Katznelson L, Laws ER, Melmed S, et al. Acromegaly: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2014;99(11):3933-3951. doi: https://doi.org/10.1210/jc.2014-2700

24. Vilar L, Freitas MC, Naves LA, et al. Diagnosis and management of hyperprolactinemia: Results of a Brazilian multicenter study with 1234 patients. J Endocrinol Invest. 2008;31(5):436-444. doi: https://doi.org/10.1007/BF03346388

25. Mel’nichenko GA, Dzeranova LK, Pigarova EA, et al. Russian association of endocrinologists national practice guidelines (clinical signs, diagnosis, differential diagnosis, treatment). Hyperprolactinemia. Problems of Endocrinology. 2013;59(6):19-26. (In Russ.) doi: https://doi.org/10.14341/probl201359619-26