Lesson
Axis Physiology and Pituitary Assessment
Pituitary reasoning begins with an axis map. Hormone concentration, target-gland response, feedback, timing, tumor size, and visual anatomy must be interpreted together.
- Hypothalamic signals
- Anterior and posterior pituitary
- Feedback and pulsatility
- Hormone excess and deficiency
- Mass effect and visual fields
CRH, TRH, GnRH, GHRH, somatostatin, and dopamine
ACTH, TSH, LH, FSH, GH, prolactin, and posterior release
Cortisol, thyroid hormone, gonadal steroids, IGF-1, and water balance
Map each functional axis
CRH drives ACTH and cortisol, TRH supports TSH and thyroid hormone, GnRH pulses regulate LH and FSH, and GHRH and somatostatin balance GH and IGF-1. Hypothalamic dopamine tonically restrains prolactin. Arginine vasopressin and oxytocin are synthesized in hypothalamic nuclei and released from posterior pituitary terminals. A sellar lesion can therefore cause hormone excess, deficiency, or both.
Interpret patterns instead of isolated values
Pituitary hormones can be pulsatile, circadian, stress responsive, sex and age dependent, or altered by pregnancy, illness, nutrition, kidney function, and medication. Central deficiency may present with a target hormone that is low while the pituitary hormone is low or inappropriately normal. A result within the laboratory range can still be physiologically inappropriate.
Evaluate the whole gland and the surrounding anatomy
A pituitary mass assessment includes symptoms of hormone excess and deficiency, prolactin and IGF-1, adrenal and thyroid axes, gonadal function when relevant, pregnancy context, medication review, dedicated MRI, and formal visual fields when the optic apparatus is threatened. Headache, diplopia, sudden visual loss, altered mental status, or hemodynamic instability changes the timeline.
Protect the adrenal axis first
When central adrenal insufficiency and central hypothyroidism may coexist, establish glucocorticoid coverage before starting or increasing levothyroxine. Thyroid hormone can increase cortisol clearance and metabolic demand and may precipitate adrenal crisis. Dynamic testing, timing, acute illness, exogenous corticosteroids, and assay interference must be considered before declaring an axis intact.
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Lesson
Acromegaly Diagnosis and Pharmacotherapy
Growth hormone excess drives IGF-1, progressive tissue overgrowth, metabolic disease, sleep apnea, cardiovascular burden, arthropathy, and tumor effects. Treatment controls both biochemistry and the tumor.
- IGF-1 and diagnosis
- Transsphenoidal surgery
- Somatostatin receptor ligands
- GH receptor antagonism
- Monitoring and comorbidity
Remove resectable tumor and decompress threatened anatomy
Injectable or oral ligands lower GH with product-specific use
Pegvisomant lowers IGF-1 despite persistent GH secretion
Use IGF-1 in clinical context
In a patient with typical features, the 2024 consensus supports IGF-1 above 1.3 times the age-adjusted upper limit of normal as confirming acromegaly. Repeat equivocal IGF-1 with the same validated assay and consider an oral glucose tolerance test when uncertainty remains. Random GH can inform prognosis but is not required for diagnosis. MRI follows biochemical evidence rather than replacing it.
Place surgery at the center of resectable disease
Experienced transsphenoidal surgery is generally first treatment for a resectable GH-secreting pituitary tumor and can decompress the optic apparatus while offering remission. Residual or unresectable disease can require repeat surgery, medical therapy, radiation, or combinations. Follow IGF-1, tumor imaging, symptoms, and systemic complications over time.
Suppress secretion through somatostatin receptors
Octreotide and lanreotide primarily use SSTR2 signaling to reduce GH. Pasireotide has broader receptor binding, including strong SSTR5 activity, but carries substantial dysglycemia risk. Oral octreotide capsules are maintenance therapy for patients who responded to and tolerated octreotide or lanreotide and require strict empty-stomach administration. Paltusotine is an oral nonpeptide SSTR2 agonist for adults with inadequate surgical response or when surgery is not an option, with its own fasting and interaction instructions.
Block action when secretion remains uncontrolled
Pegvisomant antagonizes the GH receptor and is titrated to age-adjusted IGF-1, not GH, because some GH assays cross-react and GH remains elevated. Monitor liver tests, injection sites, glucose-lowering needs, and residual tumor by imaging. Cabergoline can lower GH in selected mild disease but is off label for acromegaly in the United States. Treatment success includes comorbidity control, not a laboratory value alone.
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Lesson
Hyperprolactinemia and Prolactinoma
Prolactin rises from autonomous secretion, stalk disruption, medication, pregnancy, hypothyroidism, kidney disease, or assay effects. The cause determines whether dopamine agonist therapy is appropriate.
- Dopamine and lactotrophs
- Differential diagnosis
- Macroprolactin and hook effect
- Cabergoline
- Surgery, fertility, and pregnancy
Pregnancy, stress, macroprolactin, dilution, and assay fit
Medication, hypothyroidism, kidney disease, and stalk effect
Cabergoline lowers secretion and usually reduces tumor volume
Start with dopamine physiology and a broad differential
Tuberoinfundibular dopamine activates lactotroph D2 receptors and suppresses prolactin release. Pregnancy and lactation, stress, sleep, chest-wall stimulation, primary hypothyroidism, kidney or liver disease, stalk compression, and many antipsychotic, antiemetic, antidepressant, opioid, estrogen, and other drugs can increase prolactin. Repeat an unexpected result under appropriate conditions and obtain a pregnancy test when relevant.
Resolve laboratory and imaging discordance
Macroprolactin can produce a laboratory elevation with limited bioactivity, while the high-dose hook effect can artifactually lower a very high prolactin result in a large tumor. Ask the laboratory for macroprolactin evaluation or serial dilution when the phenotype, value, and mass do not agree. Stalk effect usually produces a different biochemical context from a large secreting prolactinoma.
Use cabergoline as the preferred dopamine agonist
Cabergoline is a long-acting ergot-derived D2 agonist that usually lowers prolactin, restores gonadal function, and shrinks tumor. Start low, titrate to prolactin and tumor response, and monitor nausea, orthostasis, headache, psychiatric symptoms, impulse-control effects, and dose-related valvular risk. The 2023 consensus also supports discussing expert surgery for selected well-circumscribed lesions rather than presenting lifelong medication as the only option.
Plan withdrawal, fertility, and pregnancy deliberately
A carefully selected patient with sustained biochemical control and marked tumor reduction may attempt dopamine agonist withdrawal with follow-up. Fertility can return before menses normalize. Pregnancy planning depends on tumor size, invasion, symptoms, prior surgery, and treatment response. Most routine prolactin measurements are not useful during pregnancy, while new headache or visual symptoms require urgent assessment.
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Lesson
Hypopituitarism and Hormone Replacement
Replacement follows physiologic priority rather than a fixed list. Cortisol safety comes first, while each central deficiency requires a target that does not depend on a failing pituitary signal.
- Central adrenal insufficiency
- Central hypothyroidism
- Central hypogonadism
- Growth hormone deficiency
- Sequence and reassessment
Glucocorticoid coverage and emergency stress planning
Free T4, sex steroids, fertility therapy, and clinical goals
Retest after surgery, tumor response, radiation, and illness
Make glucocorticoid safety the first priority
Central adrenal insufficiency can cause fatigue, weight loss, nausea, hypoglycemia, hyponatremia, hypotension, and crisis, often without the hyperkalemia expected in primary adrenal failure because aldosterone is usually preserved. Use physiologic hydrocortisone or an equivalent regimen, teach sick-day dosing and emergency injection, and give stress doses for major illness or surgery.
Target free T4 in central hypothyroidism
Levothyroxine treats central hypothyroidism, but TSH cannot be used as the dose target. After glucocorticoid sufficiency is established, titrate using free T4, symptoms, age, cardiac risk, pregnancy context, adherence, and interactions. A suppressed TSH can be expected and does not independently prove overtreatment in central disease.
Individualize gonadal and growth hormone replacement
Central hypogonadism requires sex, age, fertility goals, pregnancy potential, bone health, thrombosis risk, cancer history, and patient preference. Gonadotropins or pulsatile GnRH may be needed for fertility rather than sex steroid replacement alone. Adult GH deficiency requires validated testing in context and cautious dose titration to clinical response and age-adjusted IGF-1, with attention to edema, arthralgia, carpal tunnel symptoms, glucose, and contraindications.
Reassess axes as the anatomy changes
Surgery, radiation, apoplexy, tumor growth, and effective tumor treatment can create, reveal, or reverse deficiencies. Reassess all relevant axes after pituitary surgery and periodically after radiation or major tumor response. Medication reconciliation must include exogenous glucocorticoids, opioids, antiepileptics, estrogen route, supplements, and agents that alter thyroid-binding proteins or hormone metabolism.
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Lesson
Arginine Vasopressin Deficiency and Desmopressin
Arginine vasopressin deficiency causes hypotonic polyuria and compensatory thirst. Desmopressin restores antidiuresis but can cause dangerous hyponatremia when intake exceeds renal water excretion.
- Water-balance physiology
- Diagnostic differentiation
- Desmopressin routes
- Hyponatremia prevention
- Postoperative water disorders
Measure urine volume and concentration and exclude solute diuresis
Use product-specific desmopressin dose, route, and timing
Monitor sodium and allow retained water to clear when appropriate
Trace water balance from osmolality to aquaporin
Hypothalamic osmoreceptors and baroreceptors regulate arginine vasopressin release. V2 receptor signaling in the collecting duct inserts aquaporin-2 channels and concentrates urine. Deficiency produces high-volume dilute urine, rising serum osmolality or sodium when water access is limited, and intense thirst when the thirst mechanism is intact.
Prove hypotonic polyuria before naming the disorder
Quantify urine volume and urine osmolality, then exclude hyperglycemia, osmotic diuresis, diuretics, hypercalcemia, hypokalemia, kidney disease, and excess intake. Water deprivation and desmopressin testing or stimulated copeptin can distinguish arginine vasopressin deficiency, renal resistance, and primary polydipsia in specialized settings. Never perform water deprivation casually in a patient who cannot maintain hydration.
Treat with product-specific desmopressin
Desmopressin is a V2-selective analogue available in several formulations with different potency, absorption, indications, and dose units. Routes are not directly interchangeable. Individualize timing around nocturia, daytime function, residual secretion, thirst, kidney function, and the ability to drink. Allow periodic breakthrough urination when appropriate so retained free water can be excreted.
Prevent water intoxication
Excess fluid intake during sustained antidiuresis can cause weight gain, headache, nausea, confusion, seizure, coma, or respiratory arrest from hyponatremia. Teach fluid guidance, symptom recognition, sodium monitoring, and temporary interruption during vomiting, diarrhea, fever, extreme heat, vigorous exercise, or other conditions that disrupt fluid balance. Postoperative patients can transition from transient deficiency to SIADH and back again, so fixed early dosing can be hazardous.
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Lesson
Sellar Emergencies, Surgery, and Longitudinal Safety
Pituitary care can change from chronic endocrine management to a neurologic and hemodynamic emergency. Visual compromise, apoplexy, adrenal failure, and postoperative water shifts demand coordinated action.
- Pituitary apoplexy
- Visual compromise
- Perioperative hormones
- Postoperative monitoring
- Longitudinal tumor and axis care
Sudden headache, visual loss, ophthalmoplegia, and instability
Stress-dose steroid and urgent multidisciplinary evaluation
Urine, sodium, vision, imaging, and every pituitary axis
Recognize pituitary apoplexy
Acute hemorrhage or infarction in a pituitary lesion can cause sudden severe headache, visual field loss, reduced acuity, ophthalmoplegia, meningismus, altered consciousness, and acute ACTH deficiency. Obtain urgent endocrine, neurosurgical, ophthalmologic, and imaging evaluation. Give stress-dose glucocorticoid promptly when adrenal insufficiency or hemodynamic instability is suspected.
Use anatomy and function to determine urgency
Formal visual fields are required when a lesion abuts or compresses the optic apparatus. Progressive visual deficit, neurological compromise, apoplexy with visual disturbance, or selected hypersecreting tumors can require surgery. Prolactinoma is a major exception because dopamine agonist therapy can rapidly reduce prolactin and tumor volume in many patients.
Monitor the postoperative sequence
Track cortisol, free T4, sodium, urine volume, urine concentration, thirst, intake, and neurological status. Early arginine vasopressin deficiency can resolve, be followed by delayed SIADH, and occasionally recur. Avoid automatic scheduled desmopressin during unstable early physiology. Reassess pituitary axes beginning around six weeks after surgery and periodically thereafter.
Build a lifelong surveillance record
Record tumor type, pathology, residual anatomy, visual findings, surgery, radiation, medical therapy, hormone excess, deficiencies, replacement doses, emergency education, fertility and pregnancy plans, bone and metabolic health, and imaging schedule. Radiation-related deficiencies can emerge years later, while effective therapy can restore some axes and alter replacement needs.
Quick check
Module test
Check the connections.
Each attempt draws 10 questions from the complete 100 question bank.
Each attempt draws a fresh set and rearranges the answer choices.
References
Current clinical foundation.
Lecture material was synthesized with the following contemporary guidance. Verify local policy and current guidance before applying clinical information.