Endocrine Pathology I - Duker

What are the three types of extracellular signaling in the endocrine system?

Autocrine, paracrine, and endocrine.

What is feedback inhibition in endocrine signaling?

A process where target tissues secrete factors that down-regulate the hormone-producing gland's activity.

What are the general classifications of endocrine diseases?

Hormone underproduction/overproduction and diseases associated with mass lesions.

Name the major endocrine organs.

Pituitary, thyroid, parathyroids, pancreas, adrenal glands, pineal gland, and organs involved in MEN.

Which hormones does the posterior pituitary secrete?

Oxytocin and antidiuretic hormone (ADH/vasopressin).

Where are posterior pituitary hormones synthesized?

In the hypothalamus.

What are the five cell types in the anterior pituitary and the hormones they produce?

• Somatotrophs: GH
• Lactotrophs: Prolactin
• Corticotrophs: ACTH
• Thyrotrophs: TSH
• Gonadotrophs: FSH, LH

What is the most common cause of hyperpituitarism?

Pituitary adenoma.

How are pituitary adenomas classified?

By the hormone produced (e.g., ACTH-producing = corticotroph adenoma).

What is the treatment for prolactinomas?

Bromocriptine or surgery.

What condition is associated with somatotroph adenomas in adults?

Acromegaly.

What syndrome is caused by ACTH-producing pituitary adenomas?

Cushing disease.

What genetic mutation causes MEN1 syndrome?

Mutation in the MEN1 gene on chromosome 11q13.

What are the main features of hypopituitarism?

Deficiency in GH, LH/FSH, TSH, ACTH, and prolactin leading to various clinical signs (e.g., dwarfism, infertility, hypothyroidism, hypoadrenalism).

What is pituitary apoplexy?

Sudden hemorrhage or infarction of the pituitary, often with a preexisting adenoma, causing headache, visual defects, and hormonal dysfunction.

What are the causes of hyperpituitarism?

Adenomas, hyperplasia, carcinomas, hormone secretion by nonpituitary tumors, and hypothalamic disorders.

What are the causes of hypopituitarism?

Ischemic injury, surgery or radiation, inflammatory reactions, and nonfunctional pituitary adenomas.

What are the local mass effects of pituitary disease?

Radiographic abnormalities of the sella

Which cell type produces ACTH and what tumor is associated with it?

Corticotrophs; ACTH cell adenoma, associated with Cushing syndrome.

Which pituitary adenoma is associated with gigantism and acromegaly?

GH cell adenoma from somatotrophs.

What are the clinical effects of a prolactin cell adenoma?

Galactorrhea, amenorrhea, sexual dysfunction, infertility.

Which cell type produces both prolactin and GH and what is the tumor called?

Mammosomatotroph; tumor is called a mammosomatotroph adenoma.

What are the associated effects of gonadotroph adenomas?

Hypogonadism, mass effects, and hypopituitarism.

Which cell type and tumor are associated with hyperthyroidism in the pituitary?

Thyrotrophs; TSH cell adenoma.

What genetic mutation is most commonly associated with sporadic pituitary adenomas?

G-protein mutations in the alpha subunit that interfere with intrinsic GTPase activity.

Name four genes associated with familial pituitary adenomas.

MEN1, CDKN1B, PRKAR1A, AIP.

What molecular changes are associated with aggressive behavior in pituitary adenomas?

Over-expression of cyclin D1, p53 mutations, and epigenetic silencing of RB1.

How do invasive pituitary adenomas differ from typical ones?

Invasive adenomas infiltrate surrounding tissues and may be aggressive, often lacking the reticulin network.

What defines an “atypical” pituitary adenoma?

High mitotic activity and strong nuclear p53 immunoreactivity.

What is the most common type of pituitary adenoma and its effects?

Prolactinoma; causes increased prolactin, amenorrhea, galactorrhea, decreased libido, and infertility.

Besides adenomas, what other conditions can cause elevated prolactin?

Physiologic causes, certain drugs, estrogens, and renal failure.

What are treatment options for prolactinomas?

Surgery or dopamine agonists like bromocriptine.

What is a somatotropinoma and what are its clinical effects?

A GH-secreting tumor; causes gigantism in children and acromegaly in adults.

How is a somatotropinoma treated?

Surgery or somatostatin analogs (e.g., octreotide).

What hormone is overproduced in corticotroph adenomas and what condition results?

ACTH; results in hypercortisolism, also known as Cushing disease.

What are bihormonal adenomas?

Adenomas that secrete both prolactin and GH.

What percentage of pituitary tumors are non-functioning adenomas, and how do they typically present?

25–30%; typically present with mass effects.

What is another name for Multiple Endocrine Neoplasia Type 1 (MEN1)?

Wermer Syndrome.

What is the genetic cause of MEN1 syndrome?

Mutation in the MEN1 gene on chromosome 11q13.

What is the inheritance pattern of MEN1 syndrome?

Autosomal dominant.

What are the classic neuroendocrine tumors associated with MEN1?

Parathyroid adenoma, anterior pituitary adenoma, and pancreatic tumors.

What non-neuroendocrine tumors may also be seen in MEN1 syndrome?

Facial angiofibroma, meningioma, and ependymoma.

How much pituitary parenchyma must be lost to result in hypopituitarism?

At least 75%, usually due to a destructive process.

What are some common causes of hypopituitarism?

Ischemic injury, surgery, radiation, inflammatory reactions, and nonfunctional pituitary adenomas.

What types of lesions or trauma can lead to hypopituitarism?

Tumors, traumatic brain injury, pituitary apoplexy, ischemic necrosis.

Name two vascular conditions that can result in hypopituitarism.

DIC and Sheehan syndrome (postpartum necrosis of the anterior pituitary).

What is empty sella syndrome?

An enlarged, empty sella turcica often associated with loss of pituitary tissue.

How can hypothalamic lesions contribute to hypopituitarism?

They can disrupt the hypothalamic-pituitary axis leading to hormone deficiencies.

What is pituitary apoplexy?

Bleeding into or impaired blood supply of the pituitary gland, often in the presence of a tumor.

In how many cases of pituitary apoplexy is the tumor previously undiagnosed?

About 80% of cases.

What defines “apoplexy” in medical terms?

A sudden neurologic impairment, usually due to a vascular process.

What are the hallmark symptoms of pituitary apoplexy?

Sudden onset of headache, visual symptoms, altered mental status, and hormonal dysfunction.

What causes visual symptoms in pituitary apoplexy?

Involvement of the optic nerve or chiasm (causing visual acuity and field defects) and cranial nerves in the cavernous sinus (causing ocular motility dysfunction).

What are the two types of pituitary apoplexy, and how do they differ?

Hemorrhagic and ischemic, each with distinct neuroimaging findings.

What is the result of growth hormone (GH) deficiency in children?

Dwarfism.

What are the effects of LH and FSH deficiency?

Amenorrhea, infertility, and other reproductive issues.

What does TSH deficiency cause?

Hypothyroidism.

What condition results from ACTH deficiency?

Hypoadrenalism.

What is a consequence of prolactin deficiency?

Failure of postpartum lactation

What hormone is involved in posterior pituitary syndromes?

Antidiuretic hormone (ADH, also called vasopressin).

What is the function of ADH in the kidneys?

It binds to receptors on collecting duct cells and promotes water reabsorption into circulation.

What is diabetes insipidus?

A condition caused by ADH deficiency leading to loss of large volumes of dilute urine, hypernatremia, and polydipsia.

What are the two types of diabetes insipidus?

Central and nephrogenic.

What is the syndrome of inappropriate ADH secretion (SIADH)?

A condition of excessive water reabsorption causing water retention, hyponatremia, and cerebral edema

What are two causes of SIADH?

Excess ADH production by the CNS and ectopic secretion by small cell carcinoma of the lung.

What are the clinical effects of hypothalamic suprasellar tumors?

They can cause anterior pituitary hypofunction or hyperfunction and diabetes insipidus.

What are two types of hypothalamic suprasellar tumors?

Gliomas and craniopharyngiomas.

What is the growth pattern and frequency of craniopharyngiomas?

Slow-growing; accounts for 1–5% of intracranial tumors.

What is the age distribution for craniopharyngiomas?

Bimodal: most common in children (5–15 years) and older adults (45–65 years)

What is the origin of craniopharyngiomas?

Remnants of the craniopharyngeal duct and/or Rathke’s pouch.

What genetic pathway is involved in craniopharyngioma pathogenesis?

WNT signaling pathway; mutation of the gene encoding β-catenin.

What is the general prognosis for craniopharyngioma?

Usually recurrence-free with excellent survival.

What are the two histologic types of craniopharyngiomas?

Adamantinomatous and papillary.

What are the key features of adamantinomatous craniopharyngioma?

Seen in children, has squamous epithelium, wet keratin, calcifications, and cysts that contain “machine oil.”

What are the key features of papillary craniopharyngioma?

Seen in adults; lacks keratin, calcifications, and cysts.

What are fibrillary astrocytomas?

They make up 80% of adult primary brain tumors and usually originate in the cerebrum.

What are the histologic features of fibrillary astrocytomas?

Astrocytic nuclei distributed among processes of varying densities.

What are characteristics of low-grade astrocytomas?

Poorly defined infiltrative tumors with hypercellularity and nuclear pleomorphism; may grow slowly and remain static for years.

What is the mean survival time for low-grade astrocytomas?

Over 5 years.

What is WHO Grade I astrocytoma?

Pilocytic astrocytoma.

What defines a WHO Grade II astrocytoma?

Diffuse astrocytoma with nuclear atypia only.

What features are seen in WHO Grade III astrocytoma (anaplastic)?

Nuclear atypia and significantly increased proliferation activity.

What defines WHO Grade IV astrocytoma (glioblastoma multiforme)?

Nuclear atypia, high proliferation, microvascular proliferation, and/or necrosis

Where is the pineal gland located?

Near the center of the brain, between the two hemispheres, midline.

What is the average weight and shape of the pineal gland?

100–180 mg; pine-cone-shaped.

What cells make up the pineal gland?

Pinealocytes and glial cells.

What hormone is produced by the pineal gland and what is its function?

Melatonin; inhibits GnRH release.

When are blood levels of melatonin highest?

In the dark.

What endocrine condition can result from melatonin deficiency due to pineal lesions?

Precocious puberty

What neurological effect can pineal tumors cause?

Increased intracranial pressure due to mass effect.

Name three types of pineal gland lesions.

Non-neoplastic cysts, germ cell neoplasms, and pineal parenchymal tumors