The anterior pituitary constitutes about what fraction of the pituitary gland?
A. 20%
B. 40%
C. 80%
D. 95%

C. 80%

A lineage-tracing study finds stem cells expressing PIT-1. Which cell types are most directly derived from these PIT-1+ stem cells?
A. Somatotroph mammosomatotroph lactotroph
B. Corticotroph thyrotroph gonadotroph
C. Melanotroph pituicyte folliculostellate
D. Gonadotroph lactotroph corticotroph

A. Somatotroph mammosomatotroph lactotroph

During dehydration with hypovolemia, the most important physiologic function of ADH is to:
A. Increase aldosterone secretion
B. Increase cortisol secretion
C. Promote natriuresis
D. Restrict diuresis, conserve water

D. Restrict diuresis, conserve water

A 45-year-old has biochemical evidence of excess pituitary hormone output (“hyperpituitarism”). The most common underlying cause is:
A. Hypothalamic infarct
B. Anterior lobe adenoma
C. Pituitary stalk transection
D. Empty sella syndrome

B. Anterior lobe adenoma

The most common pituitary adenomas most often secrete both:
A. Growth hormone and prolactin
B. ACTH and TSH
C. LH and FSH
D. TSH and prolactin

A. Growth hormone and prolactin

A pituitary lesion measures 8 cm in greatest dimension. By size designation, this is a:
A. Carcinoma
B. Hyperplasia
C. Microadenoma
D. Macroadenoma

D. Macroadenoma

A pituitary lesion measures 0.6 cm in greatest dimension. By size designation, this is a:
A. Microadenoma
B. Macroadenoma
C. Craniopharyngioma
D. Rathke cleft cyst

A. Microadenoma

Molecular profiling of pituitary adenomas most commonly identifies alterations involving:
A. DNA mismatch repair
B. WNT signaling activation
C. G-protein pathway mutations
D. ALK gene fusions

C. G-protein pathway mutations

The α-subunit of Gs (Gsα) is encoded by:
A. MEN1 at 11q13
B. AIP at 11q13
C. PRKAR1A at 17q24
D. GNAS at 20q13

D. GNAS at 20q13

A somatotroph adenoma carries a GNAS mutation that abrogates GTPase activity of Gsα. The key downstream consequence is:
A. Reduced cAMP signaling
B. Constitutive Giα activation
C. Suppressed adenylate cyclase
D. Constitutive Gsα, excess cAMP

D. Constitutive Gsα, excess cAMP

Pituitary adenomas are usually sporadic; about what percentage arise from inherited defects (e.g., MEN1, CDKN1B, PRKAR1A, AIP)?
A. 1%
B. 10%
C. 5%
D. 25%

C. 5%

Activating mutations of which oncogene are observed in rare pituitary carcinomas?
A. HRAS
B. KRAS
C. NRAS
D. BRAF

A. HRAS

A resected pituitary tumor is composed of uniform cells arranged in sheets and cords. The typical cell shape described for pituitary adenomas is:
A. Spindle-shaped
B. Stellate
C. Columnar
D. Polygonal

D. Polygonal

A reticulin stain is used to help distinguish a pituitary adenoma from nonneoplastic anterior pituitary. A pituitary adenoma is most suggested by:
A. Dense reticulin framework
B. Absent reticulin network
C. Expanded sinusoidal network
D. Perivascular reticulin rings

B. Absent reticulin network

A subset of pituitary adenomas shows elevated mitotic activity with nuclear p53 expression. This finding most strongly correlates with mutations in:
A. TP53
B. GNAS
C. MEN1
D. AIP

A. TP53

A patient with a known pituitary adenoma develops sudden severe headache and acute worsening symptoms. This presentation is most consistent with:
A. Lactotroph hyperplasia
B. Dystrophic calcification
C. Pituitary apoplexy
D. Nelson syndrome

C. Pituitary apoplexy

A 28-year-old has amenorrhea and galactorrhea with elevated serum prolactin. The most frequent hyperfunctioning pituitary adenoma type is:
A. Somatotroph adenoma
B. Corticotroph adenoma
C. Thyrotroph adenoma
D. Lactotroph adenoma

D. Lactotroph adenoma

Histology shows chromophobic cells with juxtanuclear PIT-1 localization in a prolactin-secreting tumor. This most strongly indicates:
A. Densely granulated lactotroph adenoma
B. Sparsely granulated lactotroph adenoma
C. Silent corticotroph adenoma
D. Gonadotroph adenoma

B. Sparsely granulated lactotroph adenoma

A prolactin-secreting tumor is acidophilic and shows diffuse cytoplasmic PIT-1 localization. This best fits:
A. Densely granulated lactotroph adenoma
B. Sparsely granulated lactotroph adenoma
C. Null-cell adenoma
D. Mixed corticotroph adenoma

A. Densely granulated lactotroph adenoma

A prolactinoma contains extensive calcification with numerous psammoma bodies, forming a “pituitary stone.” This process is best termed:
A. Metastatic calcification
B. Caseous necrosis
C. Dystrophic calcification
D. Amyloid deposition

C. Dystrophic calcification

Elevated serum prolactin most classically causes which symptom pair?
A. Hypertension and hypokalemia
B. Amenorrhea and galactorrhea
C. Weight loss and tremor
D. Polyuria and polydipsia

B. Amenorrhea and galactorrhea

The diagnosis of a prolactin-secreting adenoma is made more readily in women, especially ages 20–40, most likely because:
A. Men have higher baseline prolactin
B. Women have larger pituitaries
C. Men develop symptoms earlier
D. Menses are prolactin-sensitive

D. Menses are prolactin-sensitive

Pathologic hyperprolactinemia can occur without an adenoma when loss of dopamine-mediated inhibition causes:
A. Lactotroph hyperplasia
B. Corticotroph hyperplasia
C. Somatotroph metaplasia
D. Gonadotroph atrophy

A. Lactotroph hyperplasia

A child develops excessive linear growth; an adult develops enlarged hands and jaw from the same tumor type. This is most consistent with:
A. Lactotroph adenoma
B. Thyrotroph adenoma
C. Somatotroph adenoma
D. Gonadotroph adenoma

C. Somatotroph adenoma

Hypercortisolism due to excessive ACTH production by the pituitary is specifically designated:
A. Ectopic ACTH syndrome
B. Primary adrenal Cushing
C. Pseudo-Cushing state
D. Cushing disease

D. Cushing disease

A corticotroph adenoma shows PAS positivity. This is most directly explained by carbohydrate within:
A. Prolactin
B. POMC
C. GH
D. TSH

B. POMC

After bilateral adrenalectomy performed for Cushing syndrome, a patient develops an enlarging destructive pituitary tumor. This condition is:
A. Nelson syndrome
B. Sheehan syndrome
C. Pituitary apoplexy
D. Craniopharyngioma

A. Nelson syndrome

A pituitary tumor produces no clinically apparent hormone excess. It most commonly presents due to:
A. Hyperpigmentation
B. Episodic flushing
C. Mass effects
D. Carcinoid-like diarrhea

C. Mass effects

A pituitary tumor causing ACTH-dependent hypercortisolism is evaluated at diagnosis. The most typical description is:
A. Microadenoma; basophilic, dense granules
B. Macroadenoma; acidophilic, dense granules
C. Microadenoma; chromophobic, sparse granules
D. Macroadenoma; reticulin-rich parenchyma

A. Microadenoma; basophilic, dense granules

The post-adrenalectomy pituitary tumor enlargement in Nelson syndrome most often results from:
A. New HRAS mutation
B. Loss steroid feedback on adenoma
C. Dopamine excess at lactotrophs
D. Reticulin network restoration

B. Loss steroid feedback on adenoma

A pituitary tumor is classified as carcinoma only when it shows:
A. Cavernous sinus invasion
B. Marked nuclear pleomorphism
C. Craniospinal or systemic metastases
D. Diameter greater than 1 cm

C. Craniospinal or systemic metastases

Most pituitary carcinomas are:
A. Cystic and nonsecretory
B. Inflammatory and fibrotic
C. Congenital and developmental
D. Functional and hormone-secreting

D. Functional and hormone-secreting

The most common secreted products in pituitary carcinoma are:
A. GH and TSH
B. Prolactin and ACTH
C. LH and FSH
D. ADH and oxytocin

B. Prolactin and ACTH

Postpartum necrosis of the anterior pituitary is called:
A. Nelson syndrome
B. Sheehan syndrome
C. Cushing disease
D. Empty sella syndrome

B. Sheehan syndrome

In pregnancy, anterior pituitary enlargement is vulnerable because it leads to relative:
A. Hyperperfusion
B. Venous thrombosis
C. Hypoxia
D. Cerebral edema

C. Hypoxia

Pituitary destruction by surgery or radiation can lead to:
A. Empty sella syndrome
B. Cushing disease
C. Nelson syndrome
D. Pituitary hyperplasia

A. Empty sella syndrome

Primary empty sella is most directly caused by:
A. Diaphragma sella defect
B. Pituitary stalk transection
C. Suprasellar tumor hemorrhage
D. Autoimmune hypophysitis

A. Diaphragma sella defect

Secondary empty sella most classically follows:
A. Congenital sellar defect
B. CSF overproduction
C. Mass removal or infarction
D. Dopamine agonist therapy

C. Mass removal or infarction

The most commonly implicated suprasellar tumors are:
A. Gliomas and craniopharyngiomas
B. Meningiomas and schwannomas
C. Metastases and lymphomas
D. Ependymomas and medulloblastomas

A. Gliomas and craniopharyngiomas

Craniopharyngiomas have reported abnormalities in:
A. JAK-STAT signaling
B. Hedgehog signaling
C. WNT signaling pathway
D. TGF-beta signaling

C. WNT signaling pathway

Which pairing correctly matches craniopharyngioma variant to typical age?
A. Papillary child, adamantinomatous adult
B. Adamantinomatous child, papillary adult
C. Both variants mainly neonatal
D. Both variants mainly geriatric

B. Adamantinomatous child, papillary adult

Radiologically visible calcifications are most typical of:
A. Adamantinomatous variant
B. Papillary variant
C. Both variants equally
D. Neither variant

A. Adamantinomatous variant

Calcification is only rarely seen in:
A. Adamantinomatous childhood tumors
B. Pituitary adenomas
C. Suprasellar gliomas
D. Papillary craniopharyngioma

D. Papillary craniopharyngioma

Adamantinomatous craniopharyngioma most often shows:
A. Glands with mucin pools
B. Small blue cells sheets
C. Nests cords squamous reticulum
D. Spindle cells fascicles

C. Nests cords squamous reticulum

Papillary craniopharyngioma most often shows:
A. Wet keratin nodules
B. Solid sheets and papillae
C. Rosettes with neuropil
D. Glandular acini formation

B. Solid sheets and papillae

Malignant transformation of craniopharyngioma is exceptionally rare and usually after:
A. Dopamine agonists
B. Adrenalectomy
C. Thyroid ablation
D. Irradiation

D. Irradiation

The hormone that stimulates Graafian follicles is:
A. FSH
B. LH
C. ACTH
D. TSH

A. FSH

The hormone that induces ovulation and corpus luteum formation is:
A. Prolactin
B. FSH
C. LH
D. GH

C. LH

The two hormones regulating spermatogenesis and testosterone production are:
A. ACTH and cortisol
B. FSH and LH
C. TSH and T3
D. Prolactin and oxytocin

B. FSH and LH

Transcription factors required for gonadotroph differentiation include:
A. PIT-1 and TBX19
B. PROP1 and PAX8
C. SOX2 and NKX2-1
D. SF-1 and GATA-2

D. SF-1 and GATA-2

“Mass effect” from a pituitary tumor refers to:
A. Hormone overproduction symptoms
B. Autoimmune gland destruction
C. Compression of nearby structures
D. Metastatic spread to spine

C. Compression of nearby structures

Sudden hemorrhage into a pituitary adenoma causing rapid enlargement is:
A. Sheehan syndrome
B. Pituitary apoplexy
C. Nelson syndrome
D. Empty sella syndrome

B. Pituitary apoplexy

A pituitary macroadenoma raises intracranial pressure. Typical symptoms include:
A. Fever and rash
B. Polyuria and thirst
C. Flank pain hematuria
D. Headache nausea vomiting

D. Headache nausea vomiting

A “pituitary incidentaloma” is most often a:
A. Functional macroadenoma
B. Metastatic sellar lesion
C. Silent microadenoma
D. Posterior pituitary cyst

C. Silent microadenoma

GNAS mutations have been reported to occur in:
A. Gonadotroph adenomas
B. Corticotroph adenomas
C. Lactotroph adenomas
D. Thyrotroph adenomas

B. Corticotroph adenomas

GNAS mutations are absent in thyrotroph, lactotroph, and gonadotroph adenomas because their hypothalamic hormones are not:
A. Steroid-receptor mediated
B. Tyrosine-kinase mediated
C. IP3-DAG mediated
D. cAMP-pathway mediated

D. cAMP-pathway mediated

An aggressive pituitary adenoma may show:
A. Cyclin D1 overexpression
B. APC truncation
C. BRCA2 loss
D. VHL activation

A. Cyclin D1 overexpression

Another aggressive-behavior molecular abnormality is:
A. PTEN duplication
B. Epigenetic RB silencing
C. CFTR mutation
D. ALK fusion

B. Epigenetic RB silencing

Another aggressive-behavior molecular abnormality is:
A. PAX6 loss
B. SMAD4 gain
C. KRAS deletion
D. HRAS activation

D. HRAS activation

Pituitary adenomas most commonly involve alterations in:
A. Notch signaling
B. JAK-STAT signaling
C. G-protein signaling
D. Hedgehog signaling

C. G-protein signaling

In primary empty sella, CSF herniation typically leads to:
A. Pituitary compression
B. Pituitary infarction
C. Pituitary carcinoma
D. Pituitary hyperplasia

A. Pituitary compression

Sheehan syndrome is the most common clinically significant form of:
A. Pituitary hyperplasia
B. Pituitary carcinoma
C. Posterior pituitary necrosis
D. Anterior pituitary ischemic necrosis

D. Anterior pituitary ischemic necrosis

A sellar tumor invades bone locally but has no metastases. This is not carcinoma because carcinoma requires:
A. Metastases beyond the sella
B. Tumor size over 1 cm
C. Diffuse calcification
D. High prolactin secretion

A. Metastases beyond the sella

A craniopharyngioma composed of well-differentiated squamous epithelium that usually lacks keratin, calcification, and cysts is:

A. Adamantinomatous variant
B. Suprasellar glioma
C. Papillary variant
D. Pituitary adenoma

C. Papillary variant

Which is NOT a common SIADH cause category?
A. Ectopic ADH by tumors
B. Drugs increasing ADH
C. CNS disorders
D. Pregnancy pituitary enlargement

D. Pregnancy pituitary enlargement

Which pituitary adenoma has higher risk of invasion and recurrence?
A. Atypical adenoma
B. Nonfunctioning adenoma
C. Thyrotroph adenoma
D. Microadenoma

A. Atypical adenoma

A prolactinoma is chromophobic with juxtanuclear PIT-1. Which subtype fits best?
A. Corticotroph adenoma
B. Gonadotroph adenoma
C. Thyrotroph adenoma
D. Sparsely granulated lactotroph

D. Sparsely granulated lactotroph

A prolactinoma is acidophilic with diffuse cytoplasmic PIT-1. Which subtype fits best?
A. Silent corticotroph adenoma
B. Densely granulated lactotroph
C. Null-cell adenoma
D. Gonadotroph adenoma

B. Densely granulated lactotroph

A 26-year-old has amenorrhea and high prolactin. The mechanism of amenorrhea is:
A. Direct ovarian theca toxicity
B. Prolactin suppresses GnRH release
C. Prolactin increases FSH secretion
D. LH surge becomes exaggerated

B. Prolactin suppresses GnRH release

A man with prolactinoma has no galactorrhea. Best explanation:
A. Prolactin cannot rise in men
B. Testosterone blocks prolactin receptors
C. Milk ejection requires oxytocin
D. No mammary lobules for milk

D. No mammary lobules for milk

A man with prolactinoma reports low libido. Most direct endocrine basis:
A. Low LH/FSH, low testosterone
B. High TSH, low T4
C. High ACTH, high cortisol
D. High GH, low IGF-1

A. Low LH/FSH, low testosterone

A man with a large prolactinoma has headaches. Best explanation:
A. Prostaglandin-mediated pain
B. Meningeal infection
C. Mass effect compression
D. Autoimmune vasculitis

C. Mass effect compression

Which finding is a common clinical course of lactotroph adenomas?
A. Increased serum prolactin
B. Hypercalcemia episodes
C. Severe hypoglycemia spells
D. Hyperpigmentation of skin

A. Increased serum prolactin

First-line medical therapy for lactotroph adenoma most commonly is:
A. Ketoconazole
B. Desmopressin
C. Bromocriptine dopamine agonist
D. Levothyroxine

C. Bromocriptine dopamine agonist

Lactotroph hyperplasia most directly results from loss of:
A. TRH stimulation
B. Estrogen receptor signaling
C. Cortisol feedback inhibition
D. Dopamine inhibition of prolactin

D. Dopamine inhibition of prolactin

After head trauma, a patient develops hyperprolactinemia. The best mechanism is:
A. GH receptor upregulation
B. Pituitary stalk damage
C. Ovarian estrogen excess
D. Increased renal prolactin clearance

B. Pituitary stalk damage

Which exposure can cause lactotroph hyperplasia via prolactin disinhibition?
A. Beta agonists
B. ACE inhibitors
C. Dopamine receptor blockers
D. Loop diuretics

C. Dopamine receptor blockers

A pituitary tumor secretes ACTH. What adrenal change results?
A. Cortisol hypersecretion
B. Aldosterone hypersecretion
C. DHEA suppression
D. Epinephrine depletion

A. Cortisol hypersecretion

Hypercortisolism caused by pituitary ACTH excess is called:
A. Ectopic ACTH syndrome
B. Cushing disease
C. Primary adrenal Cushing
D. Pseudo-Cushing state

B. Cushing disease

A pituitary tumor shows impaired LH with predominant FSH secretion. Most likely type:
A. Lactotroph adenoma
B. Corticotroph adenoma
C. Gonadotroph adenoma
D. Thyrotroph adenoma

C. Gonadotroph adenoma

A man has low libido and a pituitary FSH-predominant tumor. The symptom is most related to:
A. Increased prolactin clearance
B. Reduced estradiol production
C. Increased cortisol production
D. Decreased testosterone levels

D. Decreased testosterone levels

A premenopausal woman has amenorrhea and a pituitary tumor secreting mostly FSH. Best diagnosis:
A. Lactotroph adenoma
B. Gonadotroph adenoma
C. Thyrotroph adenoma
D. Somatotroph adenoma

B. Gonadotroph adenoma

A pituitary adenoma secreting TSH is best termed:
A. Corticotroph adenoma
B. Gonadotroph adenoma
C. Thyrotroph adenoma
D. Lactotroph adenoma

C. Thyrotroph adenoma

A “silent” anterior pituitary tumor most often presents with:
A. Mass effect symptoms
B. Episodic flushing
C. Refractory hypoglycemia
D. Carcinoid-like diarrhea

A. Mass effect symptoms

The posterior pituitary is usually spared in Sheehan syndrome because it has:
A. Lymphatic drainage dominance
B. Portal venous-only supply
C. Direct arterial blood supply
D. Exclusive CSF diffusion supply

C. Direct arterial blood supply

A sellar cyst is lined by ciliated cuboidal epithelium with goblet cells. Diagnosis:
A. Rathke cleft cyst
B. Craniopharyngioma
C. Pituitary adenoma
D. Arachnoid cyst

A. Rathke cleft cyst

Rathke cleft cysts can cause hypopituitarism mainly by:
A. ACTH hypersecretion
B. Dopamine hypersecretion
C. TSH hypersecretion
D. Compressing gland after expansion

D. Compressing gland after expansion

Hypothalamic lesions can cause diabetes insipidus by:
A. Diminishing ADH secretion
B. Increasing aldosterone secretion
C. Increasing cortisol secretion
D. Enhancing ANP release

A. Diminishing ADH secretion

Which benign tumor is a classic hypothalamic/suprasellar cause of hypopituitarism?
A. Hemangioblastoma
B. Schwannoma
C. Craniopharyngioma
D. Medulloblastoma

C. Craniopharyngioma

Hypothalamic metastases most commonly originate from:
A. Colon and pancreas
B. Breast and lung
C. Prostate and bladder
D. Ovary and cervix

B. Breast and lung

Hypothalamic insufficiency can follow irradiation of:
A. Thyroid tumors only
B. Pituitary microadenomas only
C. Adrenal tumors only
D. Brain or nasopharyngeal tumors

D. Brain or nasopharyngeal tumors

Which two diseases can involve hypothalamus causing AP deficits plus diabetes insipidus?
A. Graves and Hashimoto
B. Crohn and ulcerative colitis
C. Sarcoidosis and TB meningitis
D. Hepatitis and cirrhosis

C. Sarcoidosis and TB meningitis

Congenital deficiency of PIT-1 most classically causes deficiency of:
A. GH prolactin TSH
B. ACTH ADH oxytocin
C. LH FSH TSH
D. GH ACTH LH

A. GH prolactin TSH

SIADH causes hyponatremia primarily because ADH:
A. Wastes sodium in urine
B. Increases free water reabsorption
C. Decreases proximal bicarbonate
D. Increases plasma oncotic pressure

B. Increases free water reabsorption

The malignant neoplasm most classically causing ectopic ADH is:
A. Renal cell carcinoma
B. Hepatocellular carcinoma
C. Colon adenocarcinoma
D. Small-cell lung carcinoma

D. Small-cell lung carcinoma

Which is a common cause category of SIADH?
A. Drugs increasing ADH secretion
B. Hyperaldosteronism
C. V2 receptor loss-of-function
D. Low dietary sodium

A. Drugs increasing ADH secretion

Another common SIADH cause category is:
A. Skin blistering disorders
B. CNS disorders infection trauma
C. Bone marrow aplasia
D. GI malabsorption syndromes

B. CNS disorders infection trauma

Which finding best fits SIADH volume status?
A. Peripheral edema common
B. Hypovolemia with tachycardia
C. Hemoconcentration with high Hct
D. No peripheral edema

D. No peripheral edema

Neurologic dysfunction in SIADH is most directly driven by:
A. Renal papillary necrosis
B. Hepatic encephalopathy
C. Hyperkalemic paralysis
D. Cerebral edema

C. Hyperkalemic paralysis

A suprasellar tumor arising in the optic chiasm is most often a:
A. Glioma
B. Craniopharyngioma
C. Pituitary adenoma
D. Rathke cleft cyst

A. Glioma

A suprasellar tumor from vestigial Rathke pouch remnants is most often a:
A. Glioma
B. Meningioma
C. Craniopharyngioma
D. Schwannoma

C. Craniopharyngioma

A pituitary adenoma typically shows which cytologic pattern versus nonneoplastic parenchyma?
A. Marked pleomorphism
B. Cellular monomorphism
C. Granulomatous inflammation
D. Prominent glandular acini

B. Cellular monomorphism

Sudden hemorrhage into a pituitary adenoma causing rapid enlargement is:
A. Sheehan syndrome
B. Empty sella syndrome
C. Nelson syndrome
D. Pituitary apoplexy

D. Pituitary apoplexy