Somatotropinoma - adult disease in childhood

Background. Processes of intensive growth and development are a feature of childhood and adolescence. The speed and individuality of changes in anthropometric indicators, especially during puberty, is the reason for the difficulty of differential diagnosis of physiological growth and pathological conditions associated with diseases of the endocrine system, including pituitary adenomas that produce growth hormone (somatotropinoma), which are rare in children and young people under 19 years of age. In 2024, the International Consensus Guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence was published for the first time. It reflects data on the prevalence, clinical and genetic features, as well as approaches to the diagnosis and treatment of pituitary tumors in childhood.
Results. A clinical case of diagnosis and treatment of somatotropinoma in a 15-year-old teenage boy, who has tall relatives on his mother and father’s side, is described. The onset of the disease is in puberty. There were no complaints for a long time. An algorithm for clinical diagnosis is presented that logically substantiates the correct diagnosis and choice of treatment. Therapy for somatotropinoma was carried out in accordance with the recommendations of the international consensus, however, preoperative preparation with somatostatin analogues was not carried out, since, given the size of the macroadenoma, a decision was made on immediate surgical treatment. As a result of surgical treatment, a significant decrease in the level of growth hormone was achieved. It was noted that after 6 months the levels of IGF-1 and growth hormone remained elevated and therapy with a long-acting somatostatin analogue was justified against the background of replacement therapy for hypopituitarism, the manifestations of which persisted in the postoperative period. The patient will undergo long-term medical observation and support. The authors wanted to emphasize the likelihood of this pathology, the main aspects that make it possible to differentiate the physiological characteristics of growth in puberty from the onset of a serious illness, and recommend diagnostic algorithms at the stages of medical care.

1. Korbonits M., Blair J. C., Boguslawska A., et al. Consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: Part 2, specific diseases. Nat Rev Endocrinol. 2024; 20 (5): 290-309. DOI: 10.1038/s41574-023-00949-7.

2. Ty`rtova L. V., Olenev A. S., Parshina N. V. Pituitary gigantism. Possibilities of drug treatment. Pediatr. 2019; 10 (5): 93-99. (In Russ.)

3. Burton T., Nestour E. L., Neary M., et al. Incidence and prevalence of acromegaly in a large US health plan database. Pituitary. 2016; 19 (3): 262-267.

4. Salenave S., Boyce A. M., Collins M. T., Chanson P. Acromegaly and McCune-albright syndrome. J. Clin. Endocrinol. Metab. 2014; 99 (6): 1955-1969.

5. Kirschner L. S., Carney J. A., Pack S. D., et al. Mutations of the gene encoding the protein kinase A type I-α regulatory subunit in patients with the Carney complex. Nat. Genet. 2000; 26 (1): 89-92.

6. Trivellin G., Daly A. F., Faucz F. R., et al. Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation. N. Engl. J. Med. 2014; 371 (25): 2363-2374.

7. Srirangam Nadhamuni V., Iacovazzo D., Evanson J., et al. GHRH secretion from a pancreatic neuroendocrine tumor causing gigantism in a patient with MEN1. Endocrinol. Diabetes Metab. Case Rep. 2021: 20-0208.

8. Borson-Chazot F., Garby L., Raverot G., et al. Acromegaly induced by ectopic secretion of GHRH: a review 30 years after GHRH discovery. Ann. Endocrinol. 2012; 73 (6): 497-502.

9. Joshi К., Daly A. F., Beckers А., et al. Resistant Paediatric Somatotropinomas due to AIP Mutations: Role of Pegvisomant. Horm Res Paediatr. 2018; 90 (3): 196-202.

10. Rostomyan L., Daly A. F., Petrossians P., et al. Clinical and genetic characterization of pituitary gigantism: an international collaborative study in 208 patients. Endocrine-Related Cancer. 2015; 22 (5): 745-757.

11. George M. M., Eugster E. A., Chernausek S. D., et al. Pituitary Gigantism. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000. PMID: 25905378.

12. Personnier C., Cazabat L., Bertherat J., et al. Clinical Features and Treatment of Pediatric Somatotropinoma: Case Study of an Aggressive Tumor due to a New AIP Mutation and Extensive Literature Review. Horm Res Paediatr. 2011; 75: 392-402.

13. Mindermann T., Wilson C. B. Pediatric pituitary adenomas. Neurosurgery. 1995; 36 (2): 259-268.

14. Misra M., Cord J., Prabhakaran R., et al. Growth hormone suppression after an oral glucose load in children. J Clin Endocrinol Metab. 2007; 92 (12): 4623-4629.

15. Weber M. M., Auernhammer C. J., Lee P. D., et al. Insulin-like growth factors and insulin-like growth factor binding proteins in adult patients with severe liver disease before and after orthotopic liver transplantation. Horm. Res. 2002; 57: 105-112.

16. Haspolat K., Ece A., Gürkan F., et al. Relationships between leptin, insulin, IGF-1 and IGFBP-3 in children with energy malnutrition. Clin. Biochem. 2007; 40 (3-4), 201-205.

17. Svan H., Ritzen E. M., Hall K., et al. Estrogen treatment of tall girls: dose dependency of efects on subsequent growth and IGF-I levels in blood. Acta Paediatr. Scand. 1991; 80 (3), 328-332.

18. Famini P., Maya M. M., Melmed S. Pituitary magnetic resonance imaging for sellar and parasellar masses: ten-year experience in 2598 patients. J Clin Endocrinol Metab, 2011; 96 (6): 1633-1641.

19. Holdaway I. M., Bolland M. J., Gamble G. D. A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly. Eur J Endocrinol. 2008; 159 (2): 89-95.

20. Jane J. A. Jr., Starke R. M., Elzoghby M. A., et al. Endoscopic transsphenoidal surgery for acromegaly: remission using modern criteria, complications, and predictors of outcome. J Clin Endocrinol Metab. 2011; 96 (9): 2732-2740.

21. Minniti G., Clarke E., Scaringi C., et al. Stereotactic radiotherapy and radiosurgery for non-functioning and secreting pituitary adenomas. Rep Pract Oncol Radiother. 2016; 21 (4): 370-378.