Secreting Pituitary Adenomaspresent.pptx

SPA

1. Growth-Hormone Secreting Pituitary Adenomas Matthew-Zane Lloyd Broderick Abdul Sinan Group 3

2. CONTENTS Anatomy and Physiology of the Pituitary Gland Etiology + Epidemiology of SPA Pathophysiology Clinical Manifestations (Acromegaly, Gigantism) Diagnosis + Differentials Treatment

3. ANATOMY The pituitary gland or the hypophysis cerebri is a vital structure of the human body as it performs essential functions for sustaining life. It has the pseudonym of "the master gland." The location of the gland is within the sella turcica of the sphenoid bone. It is made up of two distinct regions called the anterior lobe and posterior lobe, which are functionally active. There is an intermediate lobe in between them. The anterior lobe secretes the majority of hormones from the pituitary gland, which are under the regulation of the hormones secreted from the hypothalamus Pituitary adenomas are benign tumors of the pituitary gland. Most are located in the anterior lobe (front portion) of the gland

4. ETIOLOGY The exact causes of pituitary adenomas are still unclear, although some researchers believe that a small percentage of cases may be genetic. Generally speaking, most tumors develop as a result of uncontrolled cellular growth caused by changes in cellular DNA. These changes may be spurred by genetics, environmental influences, certain behaviors (such as tobacco use) and other factors that are not yet fully understood. Still, pituitary adenomas have not yet been conclusively linked to any risk factors, and there is currently no way to prevent these tumors from occurring. Researchers have found that certain inherited conditions are associated with pituitary adenoma growth. These disorders include multiple endocrine neoplasia (type 1 and type 4), McCune Albright syndrome and Carney complex.

5. EPIDEMIOLOGY Pituitary adenomas make up 10% to 15% of all tumors that develop within your skull. About 77 out of 100,000 people have a pituitary adenoma, but researchers think adenomas actually occur in as many as 20% of people at some point in their lives. As many people with pituitary adenomas, especially microadenomas, are asymptomatic, they’re usually never found. Epidemiologic studies show that pituitary adenomas are increasing in incidence (between 3.9 and 7.4 cases per 100,000 per year) and prevalence (76 to 116 cases per 100,000 population) in the general population (approximately 1 case per 1000 of the general population).

6. Pathophysiology Pituitary tumors are mostly sporadic Some are genetic syndromes Endocrine neoplasia type 1 (MEN1) McCune-Albright syndrome Carney complex Monoclonal origin for genetic tumors Familial pituitary tumors resulted from germline mutations Aryl hydrocarbon receptor-interacting protein (AIP) Pituitary familial gigantism Secretory tumors most common prolactinomas Corticotropin - Cushings Growth Hormone - Acromegaly Gonadotropins TSH - Hyperthyroidism

7. Clinical Manifestations 30% of all endocrine active pituitary tumors 3rd - 5th decade presentation with macroadenomas 4 - 10 years preclinical course GH excess most common sign: Acromegaly or Gigantism Frontal bossing and prognathism m acroglossia Exaggerated acral growth Organomegaly Hypertension, Cardiomyopathy, CHF Restrictive lung diseases, Sleep apnea Arthropathies High percentage diabetes mellitus Gigantism = GH hypersecretion before fusion of long bone epiphysis, characterised by tall stature (IGF-1) Acromegaly = GH hypersecretion after fusion of epiphysis, characterised by large extremities and characteristic facies

8. Gigantism and Acromegaly

9. Diagnosis + DDx Diagnostic tests: Abnormal amounts of GH, IGF-1 Normal reference IGF-1 range = 68 – 220 ng/mL MRI or CT imaging of pituitary adenoma Normal size gland = 6mm x 10mm x 15mm Urine ACTH levels Vision testing Differentials: Pituitary Hyperplasia Acromegaloidism (normal) Soto’s syndrome Rathke cyst Meningioma Craniopharyngioma

10. Treatment Treatment aims: Tumor removal Normalise IGF-1 levels Relief symptoms Monitor acromegaly and associated comorbidities Surgical (Transsphenoidal Hypophysectomy) Excision is preferred initial treatment unless unfit for surgery Also for recurrences Transsphenoidal approach via the sphenoid sinus through nasal or sublabial removal of sellar floor Complications - Diabetes Insipidus and anterior pituitary hormone deficiencies Medical Dopamine agonists: d2 agonist Cabergoline act on somatotrophs to decreation secretion Somatostatin receptor ligands (SRL): like somatostatin, inhibits GH secretion. Octreotide + Lanreotide Radiation Therapy External radiation - 60% of patients normalise IGF-1 in 10 years Stereotactic single high dose irradiation (gamma knife) . Must limit radiation to optic chiasm

11. References Asa SL, Ezzat S. An Update on Pituitary Neuroendocrine Tumors Leading to Acromegaly and Gigantism. Journal of Clinical Medicine. 2021; 10(11):2254. https://doi.org/10.3390/jcm10112254 Osamura RY, Egashira N, Kajiya H, Takei M, Tobita M, Miyakoshi T, Inomoto C, Takekoshi S, Teramoto A. Pathology, pathogenesis and therapy of growth hormone (GH)-producing pituitary adenomas: technical advances in histochemistry and their contribution. Acta Histochem Cytochem. 2009 Aug 29;42(4):95-104. doi: 10.1267/ahc.09004. Epub 2009 Aug 11. PMID: 19759870; PMCID: PMC2742723. Pituitary Microadenomas Treatment & Management Updated: Nov 07, 2022 Author: Andre E Manov, MD, MSHM, FACP, CPE; Chief Editor: George T Griffing, MD https://emedicine.medscape.com/article/126702-treatment#d5 Larkin S, Ansorge O. Pathology And Pathogenesis Of Pituitary Adenomas And Other Sellar Lesions. [Updated 2017 Feb 15]. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK425704/ Shlomo Melmed, Ursula B Kaiser, M Beatriz Lopes, Jerome Bertherat, Luis V Syro, Gerald Raverot, Martin Reincke, Gudmundur Johannsson, Albert Beckers, Maria Fleseriu, Andrea Giustina, John A H Wass, Ken K Y Ho, Clinical Biology of the Pituitary Adenoma, Endocrine Reviews, Volume 43, Issue 6, December 2022, Pages 1003–1037, https://doi.org/10.1210/endrev/bnac010 Gandhi CD, Post KD. GH-Secreting Pituitary Adenomas. In: Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei Cancer Medicine. 6th edition. Hamilton (ON): BC Decker; 2003. Available from: https://www.ncbi.nlm.nih.gov/books/NBK12736/ Bello MO, Garla VV. Gigantism and Acromegaly. [Updated 2023 Mar 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538261/ Yazdani, Saeed & Zali, Alireza & Shahrzadi, Sohrab & Alikhani, Mazdak & Tabatabaei, Seyed. (2015). Pituitary Adenoma: Early Results after Gamma Knife Radiosurgery in Iran. Jane JA Jr, Catalino MP, Laws ER Jr. Surgical Treatment of Pituitary Adenomas. [Updated 2022 Mar 9]. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK278983/