Pituitary Gland Pathology - 2025 PDF

WE MAKE DOCTORS Pituitary Gland Disorders Dr. Edú Rafael Herrera Ríos Modified by : Dr. Rivera Ayala WE MAKE DOCTORS Objectives 1. Describe the anatomy of both glands: identify the adenohypophysis, neurohypophysis, and pars intermedia. 2. Identify the cell population of t...

WE MAKE DOCTORS Pituitary Gland Disorders Dr. Edú Rafael Herrera Ríos Modified by : Dr. Rivera Ayala WE MAKE DOCTORS Objectives 1. Describe the anatomy of both glands: identify the adenohypophysis, neurohypophysis, and pars intermedia. 2. Identify the cell population of the adenohypophysis and the hormones produced by each cell. 3. Summarize the hypothalamus-hypophysis-target gland axis (positive and negative feedback) 4. Asses the pathologies related to hypopituitarism, their etiology, pathological features, and clinical presentation. 5. Comprehend the pathology of pituitary adenomas. 6. Examine the posterior pituitary syndrome. 7. Compare and contrast diabetes insipidus with SIADH.  Pituitary Gland Greek ptuo & Latin pituita → “phlegm” – It is located within Silla Turcica – Divided into: Anterior lobe (predominant portion, approx. 80% of pituitary gland) Posterior lobe Vestigial intermediate lobe – Adult pituitary weighs approx. 600mg (range 400-900mg)  Development of Pituitary Gland – Oral Ectoderm → Anterior Pituitary gland This is in response to signaling from neuroepithelium of the ventral diancephalon The Rathke pouch is the primordium of the anterior pituitary gland – An upward invagination of this ectodermal tissue will contact the neuroectoderm of the (primordium) of the ventral hypothalamus – Neuroectoderm → third ventricle and posterior pituitary gland Shields, Rachel & Mangla, Rajiv & Almast, Jeevak & Meyers, Steven. (2015). Magnetic resonance imaging of sellar and juxtasellar abnormalities in the paediatric population: an imaging review. Insights into imaging. 6. 10.1007/s13244-015-0401-5. Pituitary Gland ( Hypophysis)  Pituitary Gland Hormone secreting cell types found in pituitary gland (5) 1. Corticotroph cells → pro-opiomelanocortin (POMC) peptides, including adrenocorticotropic hormone (ACTH) 2. Somatotroph cells → growth hormone (GH) 3. Thyrotroph cells → thyroid-stimulating hormone (TSH, thyrotropin) β-subunit 4. Gonadotroph cells → follicle-stimulating hormone (FSH) and luteinizing hormone (LH) 5. Lactotroph cells → prolactin (PRL) The anterior lobe contains Three types of basophils: two types of acidophil: Corticotrophs Somatotrophs Gonadotrophs mammotrophs—that are Thyrotrophs (named on the best visualized by basis of the hormone that they immunocytochemistry. secrete and their target organ). - best seen via special stains. Normal histology Pituitary Gland 1. Acidophils 2. Basophils 3. Chromophobes Anterior pituitary gland https://webpath.med.utah.edu/HISTHTML/NORMAL/NORM051.html Normal histology Pituitary Gland  Pars distalis Pars intermedia Pars nervosa The posterior lobe IS NOT an endocrine gland: It is a storage site for neurosecretions of neurons of the supraoptic & paraventricular nuclei of the hypothoalamus Supraoptic → Oxytocin Paraventricular→ ADH Toluidine blue stain Hypothalamus-Pituitary-Organ Axis Causes of Pituitary Masses – Most pituitary lesions (masses) are adenomas Arise from differentiated, functional cells that secrete trophic hormones: – GH, TSH, PRL, ACTH, gonadotropins (FSH & LH) – Hyperpituitarism may arise from the excess secretion of these hormones However, other situations may arise in the presence of these mass lesions: – Theses masses may be clinically non-secreting tumors – Hypopituitarism may also result from a mass lesion » Other causes of this may be ischemic lesions, radiation, surgical removal (iatrogenic), inflammation Other physiological conditions may also cause enlargement of the pituitary gland → pregnancy https://www.barrowneuro.org/resource/about -the-pituitary-gland/  MRI Pituitary Gland https://radiopaedia.org/cases/pituitary-mri- normal-study Please use this webpage as a tool to compare MRI imaging with anatomical illustration Local mass effects Macroadenoma - Hemianopia https://step1.medbullets.com/neurology/113086/vi sual-pathway Clinical Approach to Pituitary Masses  Pituitary Adenomas Hyperpituitarism: – Most commonly associated with anterior lobe adenomas – Classified based on hormonal secretion & cell type- specific transcription factors – Pituitary carcinomas and hypothalamic disorders are rare causes of hyperpituitarism Hypopituitarism – Associated with larger, non-secreting adenomas (silent) – Associated with destruction of adjacent, normal- functioning pituitary gland parenchyma Pituitary Adenomas  Pituitary Adenomas Epidemiology: – Incidentaloma: These are described as a “a previously unsuspected pituitary lesion that is discovered on an imaging study performed for an unrelated reason.” The overwhelming majority of adenomas asymptomatic and are not clinically relavent This is due to small size and insignificant natural history Daly, A. F., & Beckers, A. (2020). The Epidemiology of Pituitary Adenomas. Endocrinology and Metabolism Clinics of North America, 49(3), 347–355. https://doi.org/10.1016/j.ecl.2020.04.002  Pituitary Adenomas Epidemiology: – Incidence is 3.9 to 7.4 cases per 100,000 – Prevalence of clinically-relevant pituitary adenomas is 1 per 1000 in the general population – Most new cases are diagnosed as prolactinomas and nonfunctioning adenomas – Incidence and prevalence is increasing: Young females with microprolactinomas are the largest subgroup population  Pituitary Adenomas - Pathogenesis Activating G-protein mutations are one of the most common alterations in pituitary adenomas E.g. GNAS mutations in somatotroph cell somatic mutations → leads to constitutive activation of G sα Failure of hydrolization of GTP leads to failure of Intracellular effector turning off other Second messengers downstream events Increased downstream signaling Pituitary Adenomas - Pathogenesis  Pituitary Adenomas - Pathogenesis – Somatic GNAS mutations → approx. 40% of somatotroph cell adenomas – Activating mutations of ubiquitin-specific protease 8 (USP8) → occurs in 30% to 60% of corticotroph adenomas enhances the activity of EGFR and other pro-growth signaling pathways in pituitary adenomas – Approximately 5% of pituitary adenomas are caused by germline loss-of-function mutations  General Morphological Concepts Macroadenoma → nonfuntional Monomorphic proliferation (compare Typically well-circumscribed with normal histology) Soft appearance Typically low mitotic count In this case, this large adenoma is Little or no reticulin network invasive and has expanded beyond Immunohistochemical stains for specific the silla turcica hormones is required for identification of specific adenoma subtypes Normal histology Pituitary Adenoma  Prolactinomas (lactotroph adenomas) These are the most common type of hyperfunctioning pituitary adenoma → 30% of clinically relevant cases May be detected as microadenomas or as larger macroadenomas with mass effect symptoms These are associated with prolactenemia (see table in next slide) – Symptoms associated with prolactenemia: amenorrhea, galactorrhea, loss of libido, and infertility  Prolactinomas (lactotroph adenomas) Macroprolactinoma → size greater tan 1cm in diameter Prolactinomas (lactotroph adenomas) What do you see? Acidophils, basophils or chromophobes? https://www.pathologyoutli nes.com/topic/cnstumorpit uitaryadenoma.html Prolactinomas (lactotroph adenomas) Prolactin immunostain https://www.pathologyoutli nes.com/topic/cnstumorpit uitaryadenoma.html  Somatotroph Adenoma Second most common type of functioning pituitary adenoma – Secretes growth hormone (GH) – Adults →acromegaly – Children → gigantism Excessive GH secretion may be insidiuous – Most cases are diagnosed as macroadenomas with mass effect symptoms Somatotroph Adenoma https://my.clevelandclinic.org/he alth/diseases/17743-acromegaly  Somatotroph Adenoma – Diagnosis: Elevated Serum GH & IGF-1 levels – Excessive GH stimulates synthesis of IGF-1 from liver and systemic tissues – Measuring IGF-1 is typically the initial screening test Acromegaly → most sensitive test is Oral Glucose tolerance test (OGTT) – An OGTT with 75 g glucose is considered the gold standard for diagnosing acromegaly – This should suppress GH to a level below 1ng/mL – Failure of suppression to this level is diagnostic of acromegaly Somatotroph Adenoma GH immunostain https://www.pathologyoutlines.com/topic/cnstumorpit uitaryadenoma.html  Corticotroph Adenoma Functional Corticotroph adenoma → excessive production of ACTH – Leads to hypersecretion of cortisol from the adrenal glands – Hypercortisolism → Cushing Syndrome Corticotroph Adenoma This image represents a variant called “Crook Cell Adenoma” It is caracterized by accumulation of keratin filaments leading to a glassy hyaline appearance CAM 5.2 immunostain This subtype of corticotroph adenoma tends to have a more aggresive natural history of disease Most corticotroph adenomas are diagnosed as microadenomas These tend to be basophilic (occasionaly chromophobic) Hypopituitarism This is typically associated when there is loss of approximately 75% or more of the parenchyma of the adenohypophysis – Hypopituitarism associated with a hypothalamic origin is suspected when posterior pituitary dysfunction appears in the form of Diabetes Insipidus Most cases of hypopituitarism arise in the setting of destruction of the adenohypophysis Hypopituitarism – Types of Lesions: Tumors + other mass lesions Traumatic brain injury & subaracnoid hemorrhage Surgery or radiation (iatrogenic) Pituitary apoplexy Ischemic necrosis (Sheehan syndrome) Rathke cleft cyst Empty Sella Syndrome Hypothalamic lesions Genetic defects Hypothalamus-Pituitary-Organ Axis Hypopituitarism – Clinical presentation Will depend on which hormones are deficient: Low GH → failure of growth in children (pituitary dwarfism) Low FSH & LH → amenorrhea and infertility in woman; decreased libido, impotence and los of pubic/axillary hair in men Low TSH → hypothyroidism Low ACTH → hypoadrenalism – Also pallor due to low melanocyte-stimulating hormone (an ACTH precursor) Low Prolactin → failure of postpartum lactation Hypopituitarism Case courtesy of Dr Hani Makky Al Salam, Radiopaedia.org, rID: 8518 Sheehan Sx + pituitary apoplexy Hypopituitarism Case courtesy of Dr Ian Bickle, Radiopaedia.org, rID: 24490 The sella is empty and enlarged: it only contains CSF  Posterior Pituitary Syndromes Diabetes Insipidus – Due to antidiuretic hormone (ADH) deficiency – Clinically characterized by polyuria Lack of ADH results in inability of the kidney to reabsorb water from the urine Important to differentiate from nephrogenic diabetes – Can result from: Traumatic brain injury Tumors Imflammatory disorders Surgery/radiation (iatrogenic)  Posterior Pituitary Syndromes ADH binds to AVPR2 receptor (arginine vasopressin receptor 2) The V2 receptor is expressed in the kidney tubule, predominantly in the distal convoluted tubule and collecting ducts Colocalization of the gene for nephrogenic diabetes insipidus (DIR) and the vasopressin type 2 receptor gene (AVPR2) in the Xq28 region. van den Ouweland AM et al. Genomics 1992 Aug;13(4)1350-1352  Posterior Pituitary Syndromes Syndrome of Inappropriate ADH secretion (SIADH) – Excess ADH secretion leads to over-resorption of water → hiponatremia – Most common cause is ectopic secretion of ADH E.g. small cell carcinoma of the lung – Other causes may be related to head trauma, certain drugs (e.g., vasopressin, thiazide diuretics)  Hypothalamic Suprasellar Tumors Lesions in this area may be a cause of hypo/hyperpituitarism, diabetes insipidus, or a mixture of these presentations The most common tumors in this area are: – Gliomas – Craniopharyngioma  Craniopharyngiomas These arise from vestigial remnants of Rathke pouch Most of these are suprasellar Bimodal age distribution: – Peak incidence in childhood (5 to 15 yrs) – 2nd peak incidence in adulthood 65 yrs and older Main symptoms include visual disturbances and headaches https://www.barrowneuro.org/resource/about -the-pituitary-gland/ Craniopharyngiomas - Morphology These tend to be large → up to 3-4cm average These are typically cystic – May be solid and encapsulated, or multiloculated 2 histological variants are described: – Adamantinomatous type → more common in children – Papillary type → more common in adults Craniopharyngiomas Adantinomatous craniopharyngioma Case courtesy of Melbourne Uni Radiology Masters, Radiopaedia.org, rID: 42784 Craniopharyngiomas Papillary Craniopharyngioma Case courtesy of Assoc Prof Frank Gaillard, Radiopaedia.org, rID: 88982  Adamantinomatous Craniopharyngioma Pathogenesis: – Increased activation of Wnt signaling pathway secondary to recurrent mutations of the CTNNB1 gene (B-catenin) Histopathology: – Composed of nests/cords of squamous epithelium A palisading effect may appear in the periphery of the lesión – Compact lamellar keratin formation →”wet keratin” Adamantinomatous Craniopharyngioma Adamantinomatous Craniopharyngioma https://www.pathologyoutlines.com/topic/cnst umoradamcraniopharyngioma.html  Papillary Craniopharyngioma Pathogenesis: – Activating BRAF mutations Histopathology: – Papillary architecture – Differentiates from adamantinomatous lesions by: Lack of lamellar keratin Lack of calcification Lack of palisading effect Papillary Craniopharyngioma https://www.pathologyoutlines.com/topic /cnstumorpapcraniopharyngioma.html  Bibliography Maitra A. The Endocrine System. In: Vinay K, Abbas AK, Aster JC, eds. Robbins and Cotran Pathologic Basis of Disease. Ninth Edit. Philadelphia: Elsevier Ltd; 2015:1073-1139. U. Kaiser, K. Ho. Pituitary Physiologic and Diagnostic Evaluation. Williams Textbook of Endocrinology. Fourteenth edit. Philadelphia: Elsevier Ltd; 2016; 184-235 S. Melmed. Pituitary Masses and Tumors. Williams Textbook of Endocrinology. Fourteenth edit. Philadelphia: Elsevier Ltd; 2016; 236-302 Daly, A. F., & Beckers, A. (2020). The Epidemiology of Pituitary Adenomas. Endocrinology and Metabolism Clinics of North America, 49(3), 347–355. https://doi.org/10.1016/j.ecl.2020.04.002 Zahr R, Fleseriu M. Updates in Diagnosis and Treatment of Acromegaly. Eur Endocrinol. 2018 Sep;14(2):57-61. doi: 10.17925/EE.2018.14.2.57. Epub 2018 Sep 10. PMID: 30349595; PMCID: PMC6182922. WE MAKE DOCTORS