CNS & pituitary tumors

Sellar region tumors

Pituitary hyperplasia

Editorial Board Members: Chunyu Cai, M.D., Ph.D., Maria Martinez-Lage, M.D.
Ethar Al-Husseinawi, M.B.Ch.B., Ph.D.
Nelli S. Lakis, M.D., M.Sc.

Last author update: 1 November 2021
Last staff update: 1 November 2021

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PubMed Search: Pituitary hyperplasia[title]

Ethar Al-Husseinawi, M.B.Ch.B., Ph.D.
Nelli S. Lakis, M.D., M.Sc.
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Cite this page: Al-Husseinawi E, Lakis NS. Pituitary hyperplasia. website. Accessed September 28th, 2023.
Definition / general
Essential features
  • Nodular or diffuse hyperplasia of polymorphic acini with intact reticulin, without effacement of gland architecture
  • MRI essentially shows symmetrical and diffuse enlargement, similar intensity to gray matter (Pituitary 1999;1:169)
ICD coding
  • ICD-10: E23.7 - disorder of the pituitary gland, unspecified
  • Adenohypophysis
Pathophysiology / etiology
  • Physiologic response
    • Most common: prolactin cell hyperplasia in pregnancy and lactation, peaks immediately postpartum
    • Puberty: pituitary height peaks in the 20 - 29 year age group (F > M)
    • Elderly: nonfunctional hyperplasia due to basophil cells
      • Pars intermedia derived proopiomelanocortin (POMC) cells invasion into the neurohypophysis, women in the 50 - 59 year age group (Hormones (Athens) 2003;2:149)
  • Pathologic hyperplasia due to end organ insufficiency
    • Longstanding primary hypothyroidism causes TSH cell hyperplasia, young females
    • Gonadotroph hyperplasia and sellar expansion in primary hypogonadism due to Klinefelter or Turner syndrome
    • Polycystic ovary syndrome: hyperprolactinemia and lactotroph hyperplasia
    • ACTH cell hyperplasia due to hypocortisolism in Addison disease
    • Rare: pituitary transcription factor gene, PROP1 mutations
  • Pathologic hyperplasia associated with ectopic excess of releasing hormones
    • GH releasing hormone (GHRH) or corticotropin releasing hormone (CRH) ectopic release causing somatotroph or corticotroph hyperplasia secreted by pancreatic islet cell tumor, pheochromocytoma, bronchial and thymic carcinoid tumors
    • ACTH cell hyperplasia due to corticotropin releasing hormone secretion from hypothalamic hamartoma or neuroendocrine tumors
  • Iatrogenic: treatment with antipsychotics and excess estrogen in transgender women are associated with increased secretion of prolactin (Int Clin Psychopharmacol 2019;34:89, Int J Mol Sci 2020;21:2024, BMJ Case Rep 2009;2009:bcr02.2009.1589)
  • Syndromic: mammosomatotroph hyperplasia in McCune-Albright syndrome, Carney complex, MEN1 related GHRH associated, X linked acrogigantism syndrome (XLAG)
  • Idiopathic
  • Hereditary (J Clin Endocrinol Metab 2011;96:E2078)
Clinical features
  • Mass effect
    • Visual disturbance, bitemporal hemianopia, diplopia
    • Headaches
  • Hormone related hyperplasia
    • GH cell: gigantism or acromegaly
    • Prolactin cell: hyperprolactinemia
    • ACTH cell: Cushing disease
    • TSH cell:
    • LH / FSH: result of early onset hypogonadism
  • Hormonal levels as indicated
Radiology description
Radiology images

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Sagittal and coronal MRI

Prognostic factors
Case reports
Gross description
  • At autopsy or in the rare event the entire gland is removed, it is diffusely enlarged and tan-white with no discernible nodules
  • Lack of well defined lesion
  • Specimen may be fragmented
Microscopic (histologic) description
  • Diffuse or nodular hyperplasia
    • Unevenly enlarged acini
    • Usually single cell type
    • Relative cellular monomorphism within affected acinus
    • Noncompressive; indistinct demarcation
    • Difficult to diagnose in fragmented specimen
    • Numerical increase in pituitary cells without alteration in architecture
    • Rare mitotic activity
  • GH cell hyperplasia: chromophobe to pale eosinophilic polygonal cells
  • PRL cell hyperplasia: chromophobe with rare microcalcifications
  • ACTH cell hyperplasia: amphophilic with large vacuoles (lysosomes) and Crooke cell change
  • TSH cell hyperplasia: chromophobe, occasional spindle cells and multiple large PAS+ lysosomes
  • LH / FSH hyperplasia: hypervacuolization (castration cells) (Endocrinol Diabetes Metab Case Rep 2015;2015:150017)
Microscopic (histologic) images

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Pituitary hyperplasia microscopic

Pituitary hyperplasia microscopic

Cytology description
  • Hypercellular smear with heterogeneous cell populations
Positive stains
  • Reticulin is essential for the diagnosis, highlights retention of acinar architecture and may show some expanded acini
  • Synaptophysin
  • Cell type routine cytoplasmic stains prolactin, GH, TSH, LH, FSH, ACTH
  • PAS highlights lysosomes in TSH hyperplasia
  • Ki67 labeling may be mildly increased (normal gland is completely negative)
Negative stains
Electron microscopy description
  • Same as normal pituitary:
    • GH producing somatotrophs:
      • Rough endoplasmic reticulum, well formed Golgi complexes and numerous large, dense secretory granules 100 - 250 nm
    • PRL producing lactotrophs:
      • Elaborate rough endoplasmic reticulum arranged in parallel arrays, occasionally forming concentric structures known as nebenkern formations
      • Prominent Golgi complexes and extrusion of secretory granules at the lateral cell borders known as misplaced exocytosis up to 700 nm
    • GH and PRL producing mammosomatotroph:
      • Pleomorphic heterogenous granules 150 - 1,000 nm and misplaced exocytosis
    • TSH producing thyrotrophs:
      • Short dilated rough endoplasmic reticulum and small secretory granules that align along the plasma membrane
    • ACTH producing corticotrophs:
      • Secretory granules are pleomorphic in shape and electron density with indentations and evaginations of granule membranes, resulting in heart and teardrop shapes
      • Also small bundles of intermediate (keratin) filaments throughout the cytoplasm
  • Reference: Ann Clin Lab Sci 1979;9:275, Microsc Res Tech 1992;20:107
Molecular / cytogenetics description
  • No specific molecular / cytogenetics available
  • Reported germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene in familiar cases
  • Some syndromic association: Carney complex, McCune-Albright syndrome, X linked acrogigantism (XLAG) and less likely, MEN1 related GHRH associated
  • Reference: J Clin Endocrinol Metab 2011;96:E2078
Sample pathology report
  • Pituitary, transsphenoidal resection:
    • Consistent with pituitary hyperplasia (see comment)
    • Comment: Histological sections of the specimen show pituitary tissue composed of unevenly enlarged acini comprised of sheets of monomorphic cells with small round nuclei and moderate amounts of granular eosinophilic cytoplasm. Immunostains were performed that show the lesional tissue cells are strongly positive for synaptophysin, chromogranin, EMA. Ki67 stain labels a rare cell. Reticulin stain highlights retention of acinar architecture and expansion of acini. Prolactin hormone is positive. Other hormonal stains (ACTH, LH, FSH, GH) are negative. This immune profile is consistent with benign pituitary hyperplasia, prolactin hormone producing. Clinical and radiological correlation are recommended.
Differential diagnosis
  • Normal adenohypophysis:
    • Normal size pituitary gland with heterogeneous cell populations within normal acini
    • ACTH cells normally aggregate at the lateral wings of anterior pituitary
  • Pituitary adenoma:
    • Enlarged mass, well defined from normal pituitary gland
    • Homogeneous cell populations with splayed and disrupted reticulin network
    • Compresses adjacent normal acini
    • Hyperplasia more likely to show strong cytoplasmic immunoreactivity to respective hormones throughout the fragments when compared with adenoma
Board review style question #1
Physiologic pituitary hyperplasia is mostly seen in

  1. Corticotrophin releasing hormone ectopic release
  2. Longstanding primary hypothyroidism
  3. Polycystic ovary syndrome
  4. Prolactin cell hyperplasia in pregnancy and lactation
Board review style answer #1
D. Prolactin cell hyperplasia in pregnancy and lactation

Comment Here

Reference: Pituitary hyperplasia
Board review style question #2
Which of the following is a characteristic microscopic feature of pituitary hyperplasia?

  1. Compresses adjacent normal acini
  2. Homogeneous cell populations with splayed and disrupted reticulin network
  3. Microcalcifications are never identified
  4. Mild acinar expansion which is noncompressive
Board review style answer #2
D. Mild acinar expansion which is noncompressive

Comment Here

Reference: Pituitary hyperplasia
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