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Chapter โ€” Pituitary Function & Pathophysiology

ASCP Board Exam ยท Lab-Focused Study Guide

Methods ยท Clinical Interpretation ยท Pre-analytical Variables ยท Practice Questions

SECTION 1 โ€” Priority Table & Quick Foundation

Topic Priority Why It’s Tested
Growth Hormone โ€” Acromegaly & OGTT suppression HIGH Definitive test (failure of GH suppression after 75โ€“100 g oral glucose) is a textbook ASCP item.
GH Deficiency โ€” Insulin Tolerance Test (ITT) cutoffs HIGH Must know glucose <40โ€“45 mg/dL, peak GH <3 ng/mL, peak cortisol <18โ€“20 ยตg/dL.
Prolactin: prolactinoma vs stalk effect vs macroprolactin vs hook effect HIGH Pre-analytical/analytical traps are the #1 prolactin exam pattern.
Diabetes Insipidus vs SIADH vs Primary Polydipsia HIGH Water deprivation + dDAVP interpretation is core knowledge.
Secondary (Central) vs Primary Hormone Deficiency HIGH Pattern: low target hormone with low/inappropriately normal pituitary hormone.
Order of hormonal loss in expanding sellar mass (GH โ†’ LH/FSH โ†’ TSH โ†’ ACTH) HIGH Classic recall item.
Sheehan syndrome, lymphocytic hypophysitis, pituitary apoplexy, empty sella MEDIUM Common case stems; pair with clinical setting.
Hypothalamic feedback loops (long / short / ultra-short, open-loop) MEDIUM Conceptual question often appears.
IGF-I / IGFBP-3 / ALS complex; Laron syndrome MEDIUM Receptor resistance traps appear in case form.
Inferior petrosal sinus sampling (Cushing’s disease) MEDIUM One sentence โ€” must recognize the indication.
Kallmann, PROP1, Pit-1 (POU1F1) mutations LOW Recognize names โ€” do not memorize molecular detail.
Exact amino-acid sequences, signaling pathway depth LOW Not tested on the MLS exam โ€” skim only.
KEY POINT โ€” Focus zone: Master (1) GH suppression with OGTT for acromegaly, (2) the four prolactin scenarios (true tumor / stalk effect / macroprolactin / hook), (3) the water-deprivation test for DI, and (4) the lab pattern of secondary deficiency (low target hormone with low/inappropriately normal pituitary hormone). Skim molecular detail, transcription factors, and exact amino-acid counts.

Quick Foundation โ€” Read this first

  • The pituitary (hypophysis) sits in the sella turcica; it has an anterior lobe (adenohypophysis, ~75% mass) from Rathke’s pouch and a posterior lobe (neurohypophysis, ~25%) from the diencephalon.
  • The hypothalamus talks to the anterior pituitary through a private blood loop โ€” the hypothalamicโ€“hypophyseal portal system.
  • Most anterior hormones are stimulated by hypothalamic releasing hormones. Prolactin is the exception โ€” it is under tonic inhibition by dopamine.
  • Anterior cells: SOmatotrophs โ†’ GH, Lactotrophs โ†’ Prolactin, Corticotrophs โ†’ ACTH, Thyrotrophs โ†’ TSH, Gonadotrophs โ†’ LH/FSH.
  • Posterior pituitary stores (not makes) ADH and oxytocin; they’re made in supraoptic & paraventricular nuclei.
  • Hormones are secreted in pulses โ€” a single random level is rarely diagnostic. Use stimulation tests for deficiency and suppression tests for excess.
  • Primary failure = high tropic hormone; secondary (pituitary) failure = LOW or inappropriately normal tropic hormone.
Analogy: Think of the hypothalamus as a thermostat, the pituitary as a transponder, and the target gland as the furnace. If the furnace is broken (primary), the thermostat (pituitary) shouts louder. If the thermostat itself is broken (secondary), the furnace stays cold but no shouting is heard.
Why it matters clinically: Every pituitary lab question is really asking “where in the loop is broken?” โ€” and the cleanest answer comes from pairing the target hormone with its tropic hormone in the same draw.
Concept Plain-English Explanation
Tropic hormone Acts on another endocrine gland (TSH โ†’ thyroid; ACTH โ†’ adrenal; LH/FSH โ†’ gonads).
Direct effector Acts on peripheral tissue directly (GH, prolactin).
Open-loop feedback Negative feedback whose set point can be MODULATED by higher input (stress, light, sex steroids).
Pulsatile secretion Hormones released in bursts โ€” between pulses the level may be undetectable.
Diurnal rhythm Time-of-day variation (ACTH/cortisol peak ~6โ€“9 a.m., nadir ~11 p.m.โ€“3 a.m.; TSH ~2ร— higher at night).
Long vs short vs ultra-short loop Long = target hormone feeds back to hypothalamus; Short = pituitary hormone feeds back to hypothalamus; Ultra-short = pituitary feeds back on itself.

SECTION 2 โ€” Core Content (Hormone by Hormone)

Growth Hormone (GH / Somatotropin)

Feature Details
Definition 191-amino-acid (22 kDa) single peptide, two intramolecular disulfide bridges; structurally related to prolactin & hPL. Half-life โ‰ˆ 15 min.
Cell source Somatotrophs (~1/3 of pituitary mass).
Regulation Stimulated by GHRH, ghrelin, sleep, exercise, stress, amino acids (arginine), hypoglycemia, sex steroids. Inhibited by somatostatin (SRIH), glucose loading, free fatty acids, glucocorticoids, IGF-I (negative feedback).
Mechanism of action Binds dimeric GHR โ†’ JAK2 tyrosine kinase โ†’ STAT5b signaling. Direct effects: lipolysis, gluconeogenesis, insulin antagonism. Indirect: stimulates hepatic IGF-I.
“Amphibolic” hormone Both anabolic (protein synthesis, +N balance) and catabolic (lipolysis, hyperglycemia).
IGF-I transport 150-kDa trimer with IGFBP-3 + acid-labile subunit (ALS) โ€” too big to cross capillaries โ†’ prevents hypoglycemia.
Excess (Acromegaly) Pituitary adenoma (somatotropinoma). Adults: coarse features, prognathism, big hands/feet, sweating, insulin resistance, hypertension, sleep apnea, โ†‘ cancer (colon). Children (before epiphyseal closure): gigantism.
Deficiency Children โ†’ growth failure. Adults โ†’ fatigue, โ†“ lean body mass, osteoporosis, โ†‘ mortality.
Definitive test for EXCESS Oral 75โ€“100 g glucose load: in normal subjects GH suppresses to <1โ€“2 ng/mL; in acromegaly GH fails to suppress (may paradoxically rise). IGF-I is the best screen.
Definitive test for DEFICIENCY Insulin tolerance test (ITT): glucose must fall <40โ€“45 mg/dL; peak GH <3 ng/mL = deficient; peak cortisol <18โ€“20 ยตg/dL = adrenal insufficiency. Alternatives: arginine + GHRH; arginine + L-DOPA.
Key interferences GH is pulsatile (random level usually low). IGF-I assays vary by age/sex. Sex-steroid priming used in peripubertal children to improve sensitivity.
PRE-ANALYTICAL โ€” GH / IGF-I: GH = pulsatile; collect basal level after overnight fast and rest. Stress, exercise, hypoglycemia, sleep can raise GH artifactually. IGF-I is more stable but is low in malnutrition, liver disease, poorly controlled diabetes, and oral estrogens. Serum (SST or red-top) is preferred; avoid hemolysis.

Prolactin (PRL)

Feature Details
Definition 199-amino-acid (23 kDa) “little” prolactin; also dimeric (~50 kDa “big”) and polymeric (โ‰ฅ150 kDa “big-big” / macroprolactin) forms.
Cell source Lactotrophs (mammotrophs); only direct-effector pituitary hormone without a tropic target.
Regulation TONIC INHIBITION by hypothalamic dopamine (PIF). Stimulated by TRH, estrogens, nipple/chest-wall stimulation, sleep, stress.
Mechanism of elevation (1) Loss of dopamine flow (stalk damage or D2 blockers), (2) Direct stimulation (TRH in primary hypothyroidism, estrogen), (3) Autonomous secretion (prolactinoma).
Clinical excess Hypogonadism (suppresses GnRH/Kiss1); women โ†’ amenorrhea, galactorrhea, infertility; men โ†’ erectile dysfunction, โ†“ libido; both โ†’ osteoporosis.
Causes of โ†‘ PRL Pregnancy, breastfeeding, stress, sleep, exercise, prolactinoma, stalk effect (any sellar mass), primary hypothyroidism (โ†‘ TRH), renal failure, PCOS, chest-wall injury, D2 antagonists (metoclopramide, phenothiazines, butyrophenones, risperidone), TCAs, ฮฑ-methyldopa, reserpine.
Numeric pattern >150โ€“200 ng/mL โ†’ almost always prolactinoma. 25โ€“100 ng/mL โ†’ stalk effect, drugs, hypothyroidism, PCOS, renal failure.
Macroprolactinemia 150-kDa IgG-bound prolactin, biologically inactive. Asymptomatic with high PRL. Detect by polyethylene glycol (PEG) precipitation โ€” recovery <40% of original = macroprolactin.
Hook (high-dose) effect Massive prolactinomas saturate both capture and signal antibodies of a sandwich immunoassay โ†’ falsely LOW result. Dilute serum 1:100 to expose the true value.
Treatment Dopamine agonist FIRST-LINE (cabergoline preferred; bromocriptine). Surgery reserved for apoplexy, vision loss, cystic tumor, drug intolerance.
PRE-ANALYTICAL โ€” Prolactin: Avoid collection after nipple/breast exam, exercise, venipuncture stress (sit quietly 30 min). Serum, ambient transport OK. Always pair with TSH and free T4 to rule out hypothyroidism. If asymptomatic high PRL โ†’ request PEG precipitation. If giant tumor with disproportionately mild PRL elevation โ†’ request 1:100 dilution to exclude hook effect.

Vasopressin (ADH) & Oxytocin

Feature Details
Structure Both are cyclic 9-amino-acid peptides with a disulfide bridge (residues 1โ€“6). Differ by only 2 amino acids. Co-synthesized with neurophysin.
Production / storage Made in supraoptic & paraventricular nuclei โ†’ transported via axons โ†’ stored in posterior pituitary.
ADH action V2 receptor in renal collecting tubules + ascending loop of Henle โ†’ adenylate cyclase โ†’ inserts aquaporin-2 โ†’ water reabsorption. V1a/V1b: vasoconstriction, ACTH release, factor VIII / vWF release.
ADH stimuli โ†‘ plasma osmolality (threshold โ‰ˆ 284 mOsm/kg) and โ†“ effective blood volume (โ‰ฅ5โ€“10% drop). Baroreceptor stimulus OVERRIDES osmotic suppression.
Diabetes Insipidus (DI) Polyuria + polydipsia + โ†‘ serum osmolality. Central = โ†“ ADH (trauma, surgery, tumor, autoimmune); Nephrogenic = V2 resistance (Liโบ, hypercalcemia, hypokalemia, gain-of-function V2 mutation in NSIAD).
SIADH Excess ADH โ†’ euvolemic HYPONATREMIA, urine osm INAPPROPRIATELY high, urine Na โ‰ฅ 40 mEq/L, serum osm < 275 mOsm/kg. Causes: ectopic ADH (small-cell lung cancer), CNS disease, drugs, post-op transient.
Drugs Treat DI: desmopressin (dDAVP). Treat SIADH (euvolemic hyponatremia): V2 antagonists โ€” conivaptan, tolvaptan.
Oxytocin Milk let-down (suckling reflex), uterine contraction (parturition). Synthetic = Pitocin. Also motherโ€“infant bonding.
PRE-ANALYTICAL โ€” ADH testing: Plasma osmolality on heparin-green or red-top, processed quickly. Water-deprivation test must be supervised (hospital setting); contraindicated if patient is already dehydrated. Pair urine osm with serum osm + serum Na in the same draw.

Tropic Hormones at a Glance (ACTH, TSH, LH, FSH)

Hormone Source / Releasing Hormone Target / Effect Feedback hormone
ACTH Corticotroph / CRH (also ADH at V1b) Adrenal cortex โ†’ cortisol; derived from POMC. Cortisol
TSH Thyrotroph / TRH (suppressed by SS, glucocorticoids) Thyroid โ†’ T4, T3 T4 / T3
LH Gonadotroph / GnRH (pulsatile) Leydig (T) / theca โ†’ androstenedione; triggers ovulation Sex steroids (E2 / T)
FSH Gonadotroph / GnRH Spermatogenesis; granulosa โ†’ estradiol via aromatase Inhibin
ฮฑ-subunit fact: TSH, LH, FSH, and hCG share an identical ฮฑ-subunit; biological specificity comes from the ฮฒ-subunit. Useful exam fact: postmenopausal hCG >5 IU/L with high FSH may be pituitary-derived hCG, not malignancy.

Hypothalamic Hormones โ€” Quick Reference

Hormone Action Size
TRH โ†‘ TSH and Prolactin 3 aa
GnRH โ†‘ LH and FSH (pulsatile) 10 aa
CRH โ†‘ ACTH 41 aa
GHRH โ†‘ GH 44 aa
Somatostatin (SRIH) โ†“ GH, โ†“ TSH, โ†“ many gut hormones 14 / 28 aa (SST-28 = major circulating form)
Dopamine (PIF) โ†“ Prolactin 1 aa (amine)

SECTION 3 โ€” Visual Memory Hooks

Mnemonic โ€” Anterior pituitary hormones (FLAT-PiG): FSH, LH, ACTH, TSH (tropic) โ€” Prolactin and GH (direct effectors).
Mnemonic โ€” Order of hormonal loss with pituitary mass (Go Look For The Adenoma Please): GH โ†’ LH/FSH โ†’ TSH โ†’ ACTH โ†’ Prolactin (PRL often โ†‘ from stalk effect, then later โ†“).
Mnemonic โ€” Causes of hyperprolactinemia (the “P” list): Pregnancy, Pill (antipsychotics), Prolactinoma, Pituitary stalk damage, Primary hypothyroidism, PCO/renal failure, Physiologic stress.
Mnemonic โ€” ADH vs Oxytocin amino acids: Both 9 aa, differ by 2. ADH = Antidiuretic โ†’ A for Arginine vasopressin.

Pattern Triggers โ€” “If you see X โ†’ think Y โ†’ because Z”

If you seeโ€ฆ Thinkโ€ฆ Becauseโ€ฆ
Coarse features + โ†‘ glove/shoe size + diabetes Acromegaly GH excess โ†’ IGF-I excess โ†’ bony & soft-tissue overgrowth + insulin antagonism.
Galactorrhea + amenorrhea + PRL > 200 ng/mL Prolactinoma True autonomous PRL secretion (>150 = tumor cutoff).
PRL 30โ€“80 ng/mL with antipsychotic, hypothyroidism, or stalk lesion Secondary hyperprolactinemia Loss of dopamine flow or โ†‘ TRH.
Asymptomatic PRL 50โ€“100 ng/mL Macroprolactinemia 150-kDa IgG-bound form; PEG precipitation excludes.
Huge pituitary tumor + “normal” PRL Hook effect Antibody saturation; dilute 1:100.
Postpartum hemorrhage + failure to lactate Sheehan syndrome Ischemic necrosis of enlarged peripartum pituitary.
Polyuria + โ†‘ serum Na after head trauma/neurosurgery Central DI ADH deficiency from stalk/hypothalamic injury.
Euvolemic โ†“ Na + concentrated urine + small-cell lung CA SIADH Ectopic ADH from tumor.
Low free T4 + low/inappropriately normal TSH Central hypothyroidism Pituitary or hypothalamic failure.
Short stature + LOW IGF-I + HIGH GH + no response to GH Laron syndrome GH receptor defect (post-receptor resistance).
Anosmia + delayed puberty + low LH/FSH Kallmann syndrome GnRH neurons failed to migrate.
Bitemporal hemianopsia Macroadenoma compressing optic chiasm Anterior chiasmal fibers cross at midline.

Commonly Confused โ€” Side-by-Side

Feature Prolactinoma Macroprolactinemia Hook Effect
Measured PRL VERY HIGH (>150 ng/mL) HIGH but symptoms absent FALSELY LOW (despite huge tumor)
Symptoms Amenorrhea / galactorrhea / mass effect Usually none Mass-effect symptoms
Form of PRL Monomeric 23 kDa 150 kDa IgG-bound Monomeric, just massive amount
Lab fix None โ€” it is real PEG precipitation Dilute 1:100
Feature Central DI Nephrogenic DI Primary Polydipsia SIADH
ADH level LOW Normal/High Suppressed HIGH (inappropriate)
Serum Na HIGH HIGH LOW-normal LOW
Serum osm HIGH HIGH LOW LOW
Urine osm (basal) LOW LOW LOW HIGH (inappropriate)
Response to dDAVP โ†‘ urine osm >50% No response No need โ€” concentrates on its own Already concentrated
Treatment dDAVP Treat cause; thiazides Restrict water intake Fluid restrict; tolvaptan/conivaptan

Diagnostic Window / Time-Based Markers

Marker Onset Peak Duration Best Clinical Use
GH (basal) Pulses every 2โ€“3 h ~90 min after sleep onset Half-life >15 min Not diagnostic alone โ€” interpret in suppression/stim context
GH after OGTT 0 min Should suppress by 60โ€“120 min 2-h test Confirm acromegaly
GH after ITT 30 min (when glucose โ‰ค40 mg/dL) ~60โ€“90 min 2-h test Diagnose GH deficiency (peak <3 ng/mL)
Cortisol after ITT 30 min ~60 min 2-h test Adrenal reserve (peak <18โ€“20 ยตg/dL = insufficiency)
ACTH diurnal Nadir 11pโ€“3a 6โ€“9 a.m. 24 h cycle Time-of-day cortisol pairing
TSH diurnal Peak at night ~2ร— daytime levels 24 h cycle Avoid using nocturnal TSH for diagnosis
LH pulse (men) โ€” Every ~55 min ~40 min peak Why a single LH is rarely diagnostic

SECTION 4 โ€” Diagnostic Flowcharts

Flowchart 1 โ€” Suspected Acromegaly

Adult with coarse features, โ†‘ glove/shoe size, sweating, HTN, diabetes โ†’ measure IGF-I (age/sex matched) FIRST.
IGF-I HIGH โ†’ proceed to oral 75โ€“100 g glucose suppression test. Measure GH at 0, 60, 120 min.
GH fails to suppress <1 ng/mL (or paradoxically rises) โ†’ Acromegaly confirmed โ†’ pituitary MRI.
Transsphenoidal adenomectomy = procedure of choice. Adjuncts: SS analogs (octreotide), dopamine agonists, pegvisomant (GHR antagonist).
โš ๏ธ Common mistake: Stopping after a random GH โ€” GH is pulsatile; high or low single values do not confirm or exclude acromegaly. Always anchor with IGF-I + OGTT.

Flowchart 2 โ€” Polyuria with Hypernatremia

Urine output > 3 L/day, serum Na rising, serum osm > 290 mOsm/kg โ†’ rule out hyperglycemia, K, Ca first.
Begin supervised water deprivation test โ†’ measure serial urine + serum osm.
Urine osm fails to rise > 300 mOsm/kg while serum osm climbs โ†’ DI confirmed.
Give dDAVP: urine osm rises > 50% โ†’ Central DI. No response โ†’ Nephrogenic DI.
Urine osm rises > 600 mOsm/kg with deprivation alone, no further dDAVP rise โ†’ Primary polydipsia.
Treat: Central โ†’ dDAVP; Nephrogenic โ†’ remove offending drug, treat hypercalcemia/hypokalemia; Primary polydipsia โ†’ restrict water.
โš ๏ธ Common mistake: Calling any polyuria “DI.” Always confirm hypernatremia and inappropriate urine dilution BEFORE starting dDAVP empirically โ€” primary polydipsia patients can develop water intoxication on dDAVP.

Flowchart 3 โ€” Elevated Prolactin (Marker Selection)

Patient with elevated PRL โ†’ review drugs, pregnancy, TSH/free T4, renal function.
PRL > 200 ng/mL + symptoms โ†’ Prolactinoma suspected โ†’ MRI sella.
PRL 25โ€“100 ng/mL + drug or hypothyroidism present โ†’ Treat reversible cause, recheck.
Asymptomatic patient with persistently high PRL โ†’ Request PEG precipitation to exclude macroprolactin.
Large pituitary mass on MRI but PRL only mildly elevated โ†’ Request 1:100 serum dilution to exclude hook effect.
True prolactinoma โ†’ cabergoline first-line; surgery for vision loss, apoplexy, cystic, drug-intolerant.
โš ๏ธ Common mistake: Calling all PRL elevations a prolactinoma. Always exclude pregnancy, hypothyroidism, drugs, macroprolactin and hook effect first.

Flowchart 4 โ€” Suspected Cushing Disease vs Ectopic ACTH

Cushing syndrome confirmed by 24-h urine free cortisol / late-night salivary / dexamethasone screen โ†’ measure plasma ACTH.
ACTH suppressed (< 5 pg/mL) โ†’ Adrenal source (NOT a pituitary problem).
ACTH normal or HIGH โ†’ ACTH-dependent. Pituitary MRI: macro lesion + classic features โ†’ Cushing disease. Negative or equivocal MRI โ†’ Inferior petrosal sinus sampling (IPSS) with CRH stimulation.
Central:peripheral ACTH ratio > 2 (basal) or > 3 (post-CRH) โ†’ Cushing disease.
Ratio < 2 โ†’ Ectopic ACTH (e.g., small-cell lung CA, carcinoid).
โš ๏ธ Common mistake: Relying on high-dose dexamethasone (~75โ€“80% specific) when IPSS is available. IPSS is the gold standard for localizing ACTH source.

Flowchart 5 โ€” Short Stature: GH Deficiency vs GH Resistance (Laron)

Child with growth velocity below age-norm โ†’ rule out malnutrition, hypothyroidism, chronic disease.
Measure IGF-I + IGFBP-3 (age/sex matched).
IGF-I LOW โ†’ measure basal GH and perform stimulation test (arginine + L-DOPA or arginine + GHRH).
Peak GH < 3โ€“5 ng/mL โ†’ GH deficiency โ€” treat with recombinant GH.
Peak GH HIGH (paradoxically) + low IGF-I + no response to GH โ†’ Laron syndrome (GHR resistance) โ€” treat with recombinant IGF-I.
โš ๏ธ Common mistake: Diagnosing GH deficiency from one random GH level โ€” and missing Laron syndrome when GH is paradoxically HIGH.

SECTION 5 โ€” 25 High-Yield Facts

# Fact
1 The anterior pituitary (~75% of mass) arises from Rathke’s pouch; the posterior pituitary (~25%) from the diencephalon.
2 Hypothalamic releasing hormones reach the anterior pituitary via the hypothalamicโ€“hypophyseal portal system.
3 Prolactin is the only anterior pituitary hormone under tonic inhibition (by dopamine); all others are stimulated.
4 TRH stimulates BOTH TSH and prolactin โ€” so primary hypothyroidism can cause hyperprolactinemia.
5 TSH, LH, FSH, and hCG share an identical ฮฑ-subunit; ฮฒ-subunit gives biological specificity.
6 Definitive test for acromegaly: oral 75โ€“100 g glucose load โ†’ GH fails to suppress <1 ng/mL.
7 IGF-I is the best SCREEN for acromegaly; oral glucose suppression is the CONFIRM.
8 IGF-I circulates in a 150-kDa trimer with IGFBP-3 + ALS โ€” this complex is too big to cross capillaries (no hypoglycemia).
9 Insulin tolerance test (ITT): glucose must fall <40โ€“45 mg/dL for stress; peak GH <3 ng/mL = deficiency, peak cortisol <18โ€“20 ยตg/dL = adrenal insufficiency.
10 Laron syndrome = GH receptor resistance โ†’ HIGH GH, LOW IGF-I, short stature, NO response to exogenous GH.
11 Prolactin > 200 ng/mL almost always = prolactinoma; 25โ€“100 ng/mL = stalk effect / drugs / hypothyroidism / renal failure.
12 Macroprolactinemia = 150-kDa biologically inactive form; detect by polyethylene glycol (PEG) precipitation.
13 Hook (high-dose) effect = massive prolactinoma producing a FALSELY LOW immunoassay result; fix with 1:100 dilution.
14 First-line therapy for prolactinoma = dopamine agonists (cabergoline preferred over bromocriptine).
15 Order of hormonal loss in expanding sellar mass: GH โ†’ LH/FSH โ†’ TSH โ†’ ACTH (mnemonic GLTAP).
16 Secondary endocrine failure pattern: LOW target hormone + LOW or inappropriately normal pituitary tropic hormone.
17 Sheehan syndrome = ischemic pituitary necrosis after postpartum hemorrhage; classic clue = failure to lactate.
18 Lymphocytic hypophysitis is autoimmune; ipilimumab (anti-CTLA-4) is the classic drug-trigger.
19 Pituitary apoplexy = acute hemorrhage into a pituitary tumor; sudden headache + visual loss + panhypopituitarism.
20 ADH (vasopressin) acts via V2 receptor โ†’ adenylate cyclase โ†’ aquaporin-2 โ†’ collecting tubule water reabsorption.
21 ADH osmotic threshold โ‰ˆ 284 mOsm/kg; baroreceptor stimulus overrides osmotic suppression.
22 Water deprivation + dDAVP differentiates central DI (responds), nephrogenic DI (no response), and primary polydipsia (concentrates without dDAVP).
23 SIADH = euvolemic hyponatremia + urine osm > serum osm + urine Na โ‰ฅ 40; treat with fluid restriction or V2 antagonist (tolvaptan/conivaptan).
24 Kallmann syndrome = GnRH deficiency with anosmia (failed neuronal migration) โ€” secondary hypogonadism, low LH/FSH.
25 Inferior petrosal sinus sampling differentiates Cushing disease (pituitary) from ectopic ACTH (central:peripheral ratio > 2 basal, > 3 after CRH = pituitary source).
EXAM TIP โ€” Single most testable pattern in this chapter: Whenever you see a sellar mass + an unusual hormone level, think in this order โ€” (1) Is the assay being tricked? (hook, macroprolactin, heterophile); (2) Is it stalk effect (loss of dopamine flow); (3) Is it reactive (TRH โ†’ PRL in hypothyroidism, ADH stress); (4) Only THEN call it autonomous tumor secretion.

Quick Interpretation Table

Lab Finding Clinical Interpretation
Low free T4 + low/inappropriately normal TSH Central (secondary) hypothyroidism โ€” pituitary failure
Random GH 12 ng/mL + symptoms of acromegaly Suggestive only โ€” must do oral glucose suppression to confirm
GH 0.8 ng/mL after 75 g glucose Normal suppression โ€” acromegaly excluded
PRL 320 ng/mL + amenorrhea + macroadenoma Prolactinoma (autonomous)
PRL 36 ng/mL + asymptomatic + normal MRI Order PEG precipitation to rule out macroprolactin
PRL 80 ng/mL on risperidone D2 antagonist-induced (drug)
Urine osm 80 + Na 152 + โ†‘ urine output Diabetes insipidus โ€” confirm with water deprivation
Serum Na 122 + urine osm 480 + urine Na 60 SIADH




SECTION 8 โ€” ๐Ÿ“– RAPID REVISION SHEET (Read 2 hours before exam)

GH Excess โ€” Acromegaly

  • Screen: IGF-I (age/sex)
  • Confirm: 75โ€“100 g OGTT โ†’ GH < 1 ng/mL = normal
  • Tx: transsphenoidal surgery
  • Gigantism = before epiphyseal closure

GH Deficiency (ITT cutoffs)

  • Glucose < 40โ€“45 mg/dL (required)
  • Peak GH < 3 ng/mL = deficient
  • Peak cortisol < 18โ€“20 ยตg/dL = adrenal insufficiency

Prolactin Numbers

  • > 200 ng/mL โ†’ prolactinoma
  • 25โ€“100 โ†’ stalk / drugs / hypothyroid / PCOS / renal
  • Macroprolactin โ†’ PEG precipitation
  • Hook effect โ†’ dilute 1:100

Pituitary Anatomy

  • Anterior = 75% (Rathke’s pouch)
  • Posterior = 25% (diencephalon)
  • Sella turcica (sphenoid)
  • Stalk = infundibulum

Order of Hormonal Loss

  • GH โ†’ LH/FSH โ†’ TSH โ†’ ACTH
  • Prolactin often rises (stalk effect)
  • Mnemonic: GLTAP

Pituitary Disasters

  • Sheehan = postpartum hemorrhage + no lactation
  • Apoplexy = hemorrhage into tumor
  • Hypophysitis = autoimmune; ipilimumab
  • Empty sella = arachnoid herniation

ADH (Vasopressin)

  • V2 โ†’ aquaporin-2 in collecting duct
  • Osmotic threshold โ‰ˆ 284 mOsm/kg
  • Baroreceptor overrides osmotic
  • 9 aa cyclic; 2 aa differ from oxytocin

DI vs SIADH (Opposites)

  • DI: โ†‘ Na, โ†‘ S-osm, โ†“ U-osm, polyuria
  • SIADH: โ†“ Na, โ†“ S-osm, โ†‘ U-osm, euvolemic
  • DI Tx: dDAVP
  • SIADH Tx: fluid restrict / tolvaptan

Water Deprivation + dDAVP

  • Central DI: dDAVP โ†‘ U-osm > 50%
  • Nephrogenic DI: no dDAVP response
  • Primary polydipsia: concentrates alone

Tropic vs Direct Effector

  • Tropic: LH, FSH, TSH, ACTH
  • Direct: GH, Prolactin
  • ฮฑ-subunit shared: TSH, LH, FSH, hCG

Hypothalamic Hormones

  • TRH โ†’ TSH + Prolactin
  • GnRH โ†’ LH + FSH
  • CRH โ†’ ACTH
  • GHRH โ†‘ / SS โ†“ GH
  • Dopamine โ†“ Prolactin

Confusing Pairs

  • Macroprolactin (high false) vs Hook (low false)
  • Kallmann (low LH/FSH) vs Klinefelter (high LH/FSH)
  • Sheehan (postpartum) vs Hypophysitis (autoimmune)
  • Primary hypothyroid (TSH โ†‘) vs Central (TSH low/normal)

Cushing Localization

  • ACTH โ†“ โ†’ adrenal
  • ACTH โ†‘ โ†’ IPSS
  • Central:peripheral > 2 basal (or >3 post-CRH) โ†’ Cushing disease

Laron vs GH Deficiency

  • Laron: GH โ†‘, IGF-I โ†“, no response to GH
  • GHD: GH โ†“, IGF-I โ†“, responds to GH
  • Treat Laron with IGF-I

Diurnal Rhythms

  • ACTH/cortisol peak 6โ€“9 a.m., nadir 11pโ€“3a
  • TSH โ‰ˆ 2ร— higher at night
  • GH peak ~90 min after sleep onset

SECTION 9 โ€” Final Memory Map

PITUITARY โ€” Hypothalamic-Hypophyseal Axis
Anatomy
โ€ข Anterior (75%, Rathke’s pouch) โ€ข Posterior (25%, diencephalon) โ€ข Sella turcica โ€ข Infundibulum (stalk) โ€ข Portal system (private blood loop)
Anterior Hormones โ€” FLAT-PiG
โ€ข FSH / LH / ACTH / TSH = tropic (target gland)
โ€ข Prolactin / GH = direct effectors
โ€ข Shared ฮฑ-subunit: TSH, LH, FSH, hCG
Growth Hormone
โ€ข GHRH โ†‘ / SS โ†“ ; ghrelin โ†‘ ; sleep, stress, AAs, hypoglycemia โ†‘
โ€ข Direct: lipolysis, gluconeogenesis, insulin antagonism
โ€ข Indirect: IGF-I (liver) โ€” circulates in 150-kDa trimer with IGFBP-3 + ALS
โ€ข Excess โ†’ Acromegaly (adults) / Gigantism (children); confirm with OGTT (no suppression)
โ€ข Deficiency โ†’ ITT (glucose <40โ€“45 โ†’ peak GH <3, cortisol <18โ€“20)
โ€ข Laron = receptor defect (HIGH GH, LOW IGF-I)
Prolactin
โ€ข Tonic inhibition by dopamine; โ†‘ by TRH, estrogen, suckling, stress
โ€ข >200 ng/mL = prolactinoma ; 25โ€“100 = drugs / stalk / hypothyroid / PCOS / renal
โ€ข Macroprolactin โ†’ PEG precipitation
โ€ข Hook effect โ†’ 1:100 dilution
โ€ข Tx: cabergoline first-line ; surgery only for vision loss / apoplexy
Posterior Pituitary
โ€ข ADH made in supraoptic/paraventricular nuclei โ†’ V2 โ†’ aquaporin-2 (collecting duct)
โ€ข Osmotic threshold โ‰ˆ 284 mOsm/kg ; baroreceptor overrides osm
โ€ข DI: โ†‘ Na, polyuria; central responds to dDAVP, nephrogenic does not
โ€ข SIADH: โ†“ Na, euvolemia, urine osm > serum osm; urine Na โ‰ฅ 40; treat with fluid restrict or V2 antagonist (tolvaptan)
โ€ข Oxytocin: milk let-down (suckling reflex), parturition, bonding
Pituitary Pathology
โ€ข Sheehan = postpartum necrosis (failure to lactate)
โ€ข Apoplexy = hemorrhage into tumor
โ€ข Lymphocytic hypophysitis (autoimmune; ipilimumab)
โ€ข Empty sella (arachnoid herniation)
โ€ข Kallmann = GnRH deficiency + anosmia
โ€ข Order of hormonal loss: GLTAP (GH โ†’ LH/FSH โ†’ TSH โ†’ ACTH โ†’ Prolactin)
Cushing Localization
โ€ข ACTH-dependent โ†’ IPSS (central:peripheral >2 basal, >3 post-CRH = pituitary)
โ€ข ACTH-independent โ†’ adrenal source
Pre-analytical Pearls
โ€ข Single GH/PRL/LH = pulsatile, rarely diagnostic
โ€ข Always pair tropic + target hormone (e.g., free T4 + TSH)
โ€ข Macroprolactin = false HIGH ; Hook effect = false LOW
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