Pituitary Gland – High-Yield Introduction (Trimmed but Complete Understanding)

The pituitary (hypophysis) sits in the sella turcica of the sphenoid bone at the base of the brain. It functions as a central endocrine controller, coordinating secretion in multiple downstream glands.

Structurally and functionally, it behaves like two endocrine organs:

1. Anterior Pituitary (Adenohypophysis)

• Receives blood via the hypophyseal portal circulation, originating in the median eminence below the hypothalamus.
• This vascular link efficiently delivers hypothalamic releasing/inhibiting hormones to anterior pituitary cells.

Major hormones released

• TSH (thyrotropin)
• ACTH
• LH
• FSH
• Prolactin
• Growth hormone (GH)

Which functions?

• Five are tropic (stimulate another gland or tissue to secrete hormones):
• TSH → thyroid
• ACTH → adrenal cortex
• LH & FSH → gonads
• GH → liver + multiple tissues (IGF-1 mediated)
• Prolactin is non-tropic, acting directly on mammary tissue for breast development and lactation.

2. Posterior Pituitary (Neurohypophysis)

• Primarily neural tissue: axon terminals whose cell bodies are in the hypothalamus.
• Stores and releases:
• Oxytocin
• Vasopressin/ADH
• Release controlled by hypothalamic neuronal firing from supraoptic + paraventricular nuclei.

3. Intermediate Lobe

• Rudimentary in humans but contains derivatives of POMC (pro-opiomelanocortin).
• Produces α-MSH and β-MSH, contributing to skin pigmentation modulation.

Why this matters

• The pituitary regulates growth, reproduction, lactation, stress response, fluid balance, and thyroid/adrenal function.
• GH will be a major focus: role in growth + potentiation of other hormone actions.

Pituitary – morphology + histology (exam-reliable compression)

GROSS ANATOMY

• Lies in sella turcica of sphenoid, connected to hypothalamus via infundibulum.
• Functionally + embryologically two major parts:

Posterior pituitary (neurohypophysis)

• Made mainly of axon terminals from:
• supraoptic nuclei → ADH
• paraventricular nuclei → oxytocin
• Develops as a down-growth of neuroectoderm from hypothalamus (neural origin).

Anterior pituitary (adenohypophysis)

• Made of hormone-secreting endocrine cells.
• Develops from Rathke pouch = ectodermal invagination of pharynx.

Intermediate lobe

• Well developed in some mammals, rudimentary in humans.
• Derived from dorsal Rathke pouch.
• In adults: closely adherent to posterior lobe, separated from anterior by residual cleft of Rathke pouch.

HISTOLOGY

Posterior pituitary

• Seen near rich vascular network.
• Contains:
• axon endings storing ADH + oxytocin in Herring bodies.
• pituicytes = stellate, modified astrocytes providing support.

Intermediate lobe (in humans)

• Mostly incorporated into anterior lobe.
• Along residual cleft: small thyroid-like follicles containing colloid of unknown function.

Anterior pituitary

• Made of interlacing cords of endocrine cells.
• Surrounded by fenestrated sinusoidal capillary network (typical endocrine pattern).
• Cells contain secretory granules released by exocytosis → capillaries → systemic circulation.

Anterior Pituitary – cell types & hormone subunits (high-yield compression)

Main secretory cell types

Identified by immunocytochemistry + EM:

1. Somatotropes → secrete growth hormone (GH)
2. Lactotropes / mammotropes → prolactin (PRL)
3. Corticotropes → ACTH
4. Thyrotropes → TSH
5. Gonadotropes → FSH + LH

Some cells contain two or more hormones.

Glycoprotein hormones – subunit concept

Hormones using 2-subunit structure:

• FSH
• LH
• TSH
• hCG (placental gonadotropin)

Key principle:

• All share a common α-subunit
• encoded by one gene
• identical amino acid sequence across hormones
• carbohydrate side-chains vary
• Each hormone has a unique β-subunit
• separate genes
• confer physiologic specificity
• α + β required for full biologic activity
• α subunits interchangeable → hybrid molecules possible

Other important cell types

• Folliculostellate cells
• extend processes between secretory cells
• release paracrine factors regulating endocrine cell growth + function
• Pituitary plasticity
• gland adjusts proportions of cell types depending on physiologic demand
• linked to a small pool of pluripotent stem cells persisting in adults

POMC & derivatives – high-yield synthesis summary

Sites of synthesis

The prohormone POMC is produced by:

• corticotropes (anterior pituitary)
• intermediate-lobe cells (when present)
• also made in hypothalamus, lung, GI tract, placenta

Signal peptide removal → formation of POMC prohormone.

Processing pathways differ by tissue

In corticotropes (anterior pituitary)

POMC hydrolysis mainly yields:

• ACTH
• β-lipotropin (β-LPH)
• small amount β-endorphin

→ these are secreted.

In intermediate-lobe cells

POMC is cleaved into:

• CLIP (corticotropin-like intermediate-lobe peptide)
• γ-LPH
• significant β-endorphin

Functions of CLIP + γ-LPH unknown.

β-endorphin is an opioid peptide; N-terminal contains amino-terminal met-enkephalin 5-residue sequence.

Melanotropins (MSH)

POMC processing also forms:

• α-MSH
• β-MSH

However:

• human intermediate lobe rudimentary
• α/β-MSH not secreted in normal adults
• in some species → melanotropins have physiologic roles (pigmentation etc.)

Control of skin coloration + pigment abnormalities (high-yield compression)

Pigment control in lower vertebrates

• Fish, reptiles, amphibians change skin color for thermoregulation, camouflage, behavioral signals.
• Mechanism: move melanin granules in/out of melanophores.
• Melanin synthesized from dopamine → dopaquinone.
• Granule movement regulated by:
• α-MSH, β-MSH
• melanin-concentrating hormone
• melatonin
• catecholamines

Pigment control in mammals/humans

• No melanophores; instead melanocytes with processes containing melanin granules.
• Melanocytes express melanotropin-1 receptors.
• Exposure to MSH increases melanin synthesis → visible pigmentation within 24 h.
• But α/β-MSH normally absent in adult circulation, physiologic role uncertain.
• However ACTH binds melanotropin-1 receptors, so ACTH can darken skin.

Endocrine pigment disorders

• Pallor → hypopituitarism (↓ ACTH).
• Hyperpigmentation → primary adrenal insufficiency
• ↑ ACTH stimulates melanotropin receptors.
• If pigmentation present, adrenal failure is NOT secondary to pituitary/hypothalamus (ACTH not high in secondary insufficiency).

Peripheral pigment abnormalities

• Albinism
• congenital inability to synthesize melanin
• due to genetic defects in pathways.
• Piebaldism
• congenital patches without pigment
• due to failed migration of neural crest melanocyte precursors
• pattern is heritable.
• Vitiligo
• acquired patchy depigmentation
• autoimmune destruction of melanocytes.

Growth Hormone – Biosynthesis, Chemistry, Species specificity (exam-ready 80%)

Genetic origin & synthesis

• GH genes are located on chromosome 17 long arm, in the GH–hCS gene cluster (5 genes)
• hGH-N → main pituitary GH
• hGH-V → variant GH, mainly placental
• 2 genes → hCS (human chorionic somatomammotropin)
• 1 pseudogene
• Pituitary-secreted GH = mixture:
• full-length hGH-N
• post-translationally modified fragments (e.g., glycosylated forms)
• splice variant lacking aa 32-46
• Physiologic significance:
• different forms share many actions
• may have opposing effects occasionally
• hard to assay individually due to structural similarity

Placental forms in pregnancy

• hGH-V + hCS secreted mainly by placenta
• circulate in significant concentrations only during pregnancy

Species specificity (VERY high-yield)

• GH structure differs significantly across species
• cross-species effectiveness varies:

→ GH action is species specific due to receptor/structural differences.

Clinical/public health relevance

• bovine GH in milk unlikely to activate human GH receptors
• GH supplements on internet used by body builders → ineffective + unsafe
• Recombinant GH given to idiopathic short stature in children → limited benefit when no GH deficiency

Growth Hormone – Plasma levels, binding, metabolism, receptors & effects (80% length)

Plasma binding + significance

• ~50% of circulating GH is protein-bound to a plasma binding protein.
• Binding protein = cleaved extracellular fragment of the GH receptor.
• Its level reflects number of GH receptors in tissues.
• Bound GH acts as reservoir buffering wide pulsatile secretion swings.

Normal plasma levels & kinetics

• Basal plasma GH (adult) <3 ng/mL (free + bound).
• GH is rapidly metabolized (mainly liver).
• Half-life 6–20 min.
• Daily GH secretion 0.2–1 mg/day.

GH receptor + signaling

• GH receptor = single-pass membrane protein (~620 aa)
• large extracellular domain
• transmembrane region
• cytoplasmic tail
• GH has two binding domains → binds first receptor, then a second → receptor homodimerization required for activation.
• Member of cytokine receptor superfamily.

Major signaling

• Activates multiple intracellular cascades—most important:
• JAK2–STAT pathway → STAT phosphorylation → STATs enter nucleus → gene activation.
• JAK-STAT also mediates prolactin + other growth factors.

Effects on growth (bone + tissues)

• Before epiphyseal fusion:
• hypophysectomy inhibits growth; GH stimulates growth.
• chondrogenesis ↑, epiphyseal plates widen, bone matrix laid → linear stature ↑.
• prolonged excess → gigantism.
• After epiphyseal closure:
• linear growth stops.
• GH excess → acromegaly:
• bone + soft tissue enlargement
• viscera ↑ size
• ↑ protein stores
• ↓ fat content.

IGF comparison – key essential table facts

(IGF-I = somatomedin C)

Key clinical hooks

• GH pulse variability → use IGF-I levels to assess GH status.
• Acromegaly/gigantism mechanism = GH excess + IGF-I mediated proliferation.
• GH excess increases lean mass, decreases fat.

Growth Hormone – Effects and Somatomedins (condensed 80%)

Protein + electrolyte metabolism

• GH = strong protein anabolic hormone

→ positive nitrogen + phosphorus balance

→ ↑ plasma phosphate

→ ↓ BUN + ↓ plasma amino acids (used for protein synthesis)

• GH deficiency in adults treated with recombinant GH →

↑ lean body mass, ↓ fat mass, ↑ metabolic rate, ↓ plasma cholesterol

• ↑ GI Ca absorption
• ↓ Na+ and K+ excretion (independent of adrenal function; ions diverted to growing tissues)
• ↑ urinary 4-hydroxyproline → marker of ↑ soluble collagen synthesis

Carbohydrate + fat metabolism

• Some GH forms are diabetogenic:

→ ↑ hepatic glucose output

→ anti-insulin effect in muscle

• GH is ketogenic and ↑ plasma free fatty acids (FFAs) hours after stimulation

→ FFAs serve as fuel during fasting/hypoglycemia/stress

• GH does not directly stimulate pancreatic β cells

but enhances β-cell responsiveness to insulinogenic stimuli (arginine, glucose)

→ indirect anabolic synergy with insulin

Somatomedins (IGFs)

• GH effects on growth, cartilage, protein synthesis mediated via somatomedins, mainly from liver + other tissues
• First identified factor = sulfation factor → name changed to somatomedin
• Major circulating somatomedins:
• IGF-I (somatomedin C)
• IGF-II
• IGFs structurally similar to insulin but retain C chain, plus D domain extension
• Relaxin family structurally related too.

Regulation + distribution

• IGF-I + IGF-II mRNAs found in many tissues (local synthesis possible)
• IGFs circulate tightly bound to IGF-binding proteins (IGFBPs)
• 6 binding proteins identified
• IGFBP-3 accounts for ~95% of circulating IGF binding

→ prolongs IGF half-life

Receptors + signaling

• IGF-I receptor ≈ insulin receptor structure + signaling
• IGF-II receptor distinct, functions in trafficking hydrolases to organelles

Roles across lifespan

• IGF-I secretion independent of GH prenatally, but stimulated by GH after birth

→ major postnatal growth factor

→ plasma levels rise in childhood → peak at puberty → decline in old age

• IGF-II largely GH-independent, major fetal growth factor

→ fetal overexpression → overgrowth of tongue, muscles, kidneys, heart, liver

In adults, IGF-II expression persists mainly in choroid plexus + meninges

Clinical significance checkpoints

• GH stimulates protein synthesis → nitrogen retention
• GH diabetogenic effects via:
• anti-insulin muscle action
• ↑ hepatic glucose output
• FFAs ↑ = major energy supply during fasting
• IGFs mediate long-term growth; GH direct metabolic effects are rapid
• Use IGF-I levels clinically to assess GH axis

Gigantism & Acromegaly

Cause

• Somatotrope pituitary adenomas → excess GH secretion.
• Before puberty → open epiphyses → gigantism (excess linear growth).
• After epiphyseal closure → acromegaly.

Clinical features of acromegaly

• Progressive enlargement: hands, feet, jaw, brow.
• Soft tissue swelling, ↑ hair growth.
• Vertebral/osteoarthritic changes.
• Organomegaly → eventual organ dysfunction → potential fatality if untreated.
• 20–40% → co-secrete prolactin.
• ~25% → abnormal glucose tolerance (insulin resistance/diabetogenic).
• 4% → galactorrhea in nonpregnant individuals.
• Rarely caused by:
• ectopic GH-secreting tumors
• hypothalamic GHRH-secreting tumors

Therapeutic Highlights

Main treatments

• Somatostatin analogues → inhibit GH secretion = first-line.
• GH receptor antagonist available → ↓ IGF-I + symptom improvement (for resistant cases).
• Pituitary tumor surgery useful for gigantism + acromegaly.
• often difficult due to tumor invasiveness.
• pharmacologic therapy commonly required post-op.

Key exam takeaways

• GH excess before vs after epiphyseal fusion → gigantism vs acromegaly.
• Progressive skeletal + soft tissue + visceral overgrowth in adults.
• Glucose intolerance + ↑ prolactin common.
• Best medical therapy = somatostatin analogues; GH receptor antagonists if refractory.
• Surgery helps but often incomplete control.

Growth Hormone – DIRECT & INDIRECT ACTIONS + CONTROL

(High-yield 80% core that gives 100% exam power)

How GH stimulates growth

1. DIRECT actions of GH

GH binds GH receptors → activates JAK–STAT signaling.

Major direct effects:

• Acts on stem/chondrocyte precursors at growth plate
• Converts stem cells → IGF-responsive cells
• Stimulates IGF-I synthesis locally in target tissues
• Anti-insulin actions peripherally:
• ↑ lipolysis
• ↓ glucose uptake in muscle/adipose
• ↑ hepatic glucose output
• → tends toward ↑ blood glucose

2. INDIRECT actions via IGF-I (somatomedin)

Locally produced + circulating IGF-I stimulates:

• cartilage proliferation
• bone formation + lengthening
• soft tissue and organ growth
• ↑ protein synthesis

Key point

GH + IGF-I work:

• together (synergy)
• independently
• both important for normal growth

Evidence:

• Inject GH into one tibial epiphysis → unilateral cartilage growth (local IGF-I)
• Infuse IGF-I into hypophysectomized animals → systemic growth restored

REGULATION OF GH SECRETION

Development pattern

Highest → adolescence

Then children → adults

Falls markedly with aging

Diurnal variation

• Low during daytime (unless triggered)
• Major pulsatile bursts at night during deep sleep

Hypothalamic control

Two main hypothalamic regulators:

• GHRH → stimulates GH
• Somatostatin → inhibits GH

Triggers increase GH by either:

• ↑ GHRH secretion
• ↓ somatostatin secretion
• or both

Peripheral regulator – Ghrelin

• secreted mainly by stomach
• also produced in hypothalamus
• potent GH stimulator
• links GH release to feeding + energy regulation

Feedback regulation

GH + IGF-I suppress further GH release:

• GH antagonizes GHRH at hypothalamus
• GH ↑ IGF-I levels
• IGF-I:
• directly inhibits GH release at pituitary
• stimulates somatostatin secretion

Clinical pearl

GH treatment increases:

• lean body mass
• reduces adipose mass

BUT

• no significant improvement in muscle strength or cognition in older adults

Growth Hormone Secretion – Stimuli

Basal features

• Normal adults: 0–3 ng/mL baseline
• Pulsatile + irregular → single samples meaningless
• Meaningful measures: 24-hr average + peak levels

STIMULI THAT ↑ GH secretion

Think “LOW fuel, HIGH demand, BRAIN activation, SEX drive”

A. Low cellular fuel triggers

Because GH mobilizes nutrients for energy.

• Hypoglycemia
• Fasting
• 2-Deoxyglucose (→ intracellular glucose deficiency)
• Exercise

Mechanism: hypothalamus ↑ GHRH + ↓ somatostatin → GH release

B. ↑ plasma amino acids

Signals recent protein intake and anabolic opportunity.

• Protein meal
• Arginine infusion (test for GH reserve)
• Other basic amino acids
• Lysine–vasopressin effect

Mechanism: amino acids + insulin drive GH for protein synthesis

C. Sleep and CNS activators

• Going to sleep (non-REM)
• L-dopa + α-agonists
• Apomorphine (dopamine agonist)
• Pyrogens (fever)
• Stress (physical + psychological)
• Glucagon test

D. Hormonal permissive stimuli

• Sex steroids (estrogen + androgens)
• Thyroid hormones (T3/T4)

Clinical: puberty GH surge + growth spurt from E2/T synergy

STIMULI THAT ↓ GH secretion

Fuel abundance + inhibitory hormones

• Glucose infusion (raises insulin → somatostatin ↑ → GH ↓)
• REM sleep (normal inhibition)
• Cortisol (catabolic, suppresses GH)
• Free fatty acids (FFA)
• Medroxyprogesterone
• GH itself + IGF-I (classical long-loop feedback)

Feedback mechanism:

IGF-I inhibits GH at both pituitary + hypothalamus (↑ somatostatin, ↓ GHRH)

Clinical testing insights

• Hypoglycemia/insulin tolerance test → provoke GH
• Arginine/arginine + insulin combo → strong GH release
• Glucose suppression → confirm GH excess (acromegaly workup)

Why these patterns make physiologic sense

• GH is a “nutrient mobilizer” for fasting/stress states

So ↓ glucose or ↑ amino acids → GH ↑ to mobilize fat + spare glucose

• When nutrients abundant, body suppresses GH to prevent unnecessary lipolysis + gluconeogenesis

→ glucose & FFAs suppress GH

• Sex steroids amplify GH so growth can occur in puberty
• Cortisol suppresses GH because it is catabolic and reduces anabolic drive

80% MASTER KEYS for exam recall

• Low glucose → GH ↑
• AA/arginine → GH ↑
• Stress/exercise/sleep onset → GH ↑
• Sex steroids/thyroid hormones permit GH action + ↑ secretion
• Glucose/FFA/cortisol/REM sleep → GH ↓
• IGF-I + GH → negative feedback

PHYSIOLOGY OF GROWTH

1. Growth is multifactorial

Postnatal growth depends on:

• Growth hormone (GH)
• Somatomedins / IGF-I
• Thyroid hormones
• Insulin
• Sex steroids: androgens + estrogens
• Glucocorticoids (excess → inhibits)
• Genetics + adequate nutrition

GH is not important for fetal growth, but is the major postnatal growth hormone.

Growth = protein accretion + ↑ length/size, not just weight gain.

2. Role of nutrition

Most important extrinsic factor.

Requirements:

• Protein
• Vitamins + minerals
• Adequate calories (protein spared from energy use)

Key concepts:

• Malnutrition early in life → ↓ linear growth
• After pubertal spurt starts, some linear growth continues even if calories ↓
• Illness/injury → stunt growth by ↑ protein breakdown (catabolism)

3. Growth periods in humans

Two main accelerated phases:

1. Infancy – continuation of fetal growth stimulus
2. Puberty – growth spurt caused by:
• GH
• Androgens
• Estrogens

Estrogen causes epiphyseal plate closure → end of growth.

Girls mature earlier → growth spurt occurs earlier.

Different tissues grow at different rates (asynchronous growth).

EXAM-CRITICAL TAKEAWAYS (memory anchors)

• GH = postnatal, not fetal
• Nutrition = #1 environmental determinant
• Sex steroids + GH drive puberty spurt
• Estrogen → growth stop via epiphyseal closure in both sexes
• Disease/injury → stunt growth by protein catabolism

HORMONAL EFFECTS ON GROWTH

GH + IGFs

• Newborns: high plasma GH
• Resting GH falls later, but pulsatile spikes increase, especially at puberty
• Mean 24-h GH:
• adults 2–4 ng/mL
• children 5–8 ng/mL
• GH → stimulates IGF-I production
• IGF-I rises through childhood → peaks at 13–17 yrs
• IGF-II remains constant postnatally

Pubertal growth spurt

• Caused by:
• GH
• IGF-I
• sex steroids (androgens + estrogens)
• Androgens: strong protein anabolic effect
• Sex steroids ↑ GH secretion → ↑ IGF-I → ↑ growth

Epiphyseal closure

• Estrogen ultimately stops linear growth by closing growth plates
• Sexual precocity → early closure → short stature
• Prepubertal castration → ↓ estrogen → delayed closure → tall stature

Thyroid hormone + GH

• Thyroid hormones = permissive for GH-mediated growth
• Alone they don’t stimulate growth
• Potentiate somatomedins
• Needed for normal GH response to hypoglycemia
• Necessary for normal ossification + skeletal maturation
• Hypothyroid children → cretinism → infantile facial/body proportions

Insulin + growth

• Insulin supports growth
• Diabetic animals fail to grow
• In GH-deficient (hypophysectomized) animals, growth occurs when insulin + adequate carbs + protein given

Adrenal hormones

• Non-androgen adrenocortical hormones: permissive (maintain BP + circulation)
• Glucocorticoids inhibit growth via direct cellular effects
• Pharmacologic steroids in children → slowed or stopped growth

Catch-up growth

• After illness/starvation, growth rate exceeds normal until original curve regained
• Mechanisms unclear

Exam keys

• GH = pulsatile + ↑ spikes at puberty
• IGF-I peak = adolescence; IGF-II stable
• Estrogen = stimulates early → closes plates later
• Sex steroids ↑ GH + IGF-I
• Thyroid hormone = permissive + skeletal maturation
• Glucocorticoids = strong growth inhibitors
• Catch-up growth = post-stress acceleration

Pituitary Gonadotropins + Prolactin

Chemistry + Structure

• FSH & LH
• Glycoproteins with α + β subunits
• Carbohydrates include: mannose, galactose, N-acetylgalactosamine, N-acetylglucosamine, fucose, sialic acid
• Carbohydrate slows clearance → ↑ potency
• Half-lives: FSH ~170 min, LH ~60 min
• FSHR mutations
• Loss-of-function → hypogonadism
• Gain-of-function → spontaneous ovarian hyperstimulation → many follicles + cytokine-mediated ↑ vascular permeability → shock risk
• Prolactin
• 199 aa, 3 disulfide bridges
• Structurally similar to GH + hCS
• Half-life ~20 min
• Also produced by endometrium + placenta

Receptors + Mechanisms

• FSH + LH receptors
• GPCR (Gs) → adenylyl cyclase → ↑ cAMP
• Extended glycosylated extracellular domain
• Prolactin receptor
• Same receptor superfamily as GH + cytokine receptors
• Dimerizes → activates JAK–STAT
• Initiates additional intracellular cascades

Pituitary Gonadotropins & Prolactin — Actions + Regulation

ACTIONS

FSH

• Required for spermatogenesis via Sertoli cell stimulation
• In females → early follicular growth

LH

• Males → Leydig stimulation → testosterone
• Females →
• Final follicle maturation
• Estrogen secretion
• Ovulation trigger
• Corpus luteum formation
• Progesterone secretion

Prolactin

• After estrogen + progesterone priming → milk secretion
• ↑ transcription of casein + lactalbumin
• Acts indirectly (not nuclear), blocked by microtubule inhibitors
• Inhibits gonadotropin effects at ovary → prevents ovulation in lactation
• Excess in males → erectile dysfunction

REGULATION OF PROLACTIN

Basal control

• Prolactin secretion is tonically inhibited by hypothalamic dopamine
• Cutting pituitary stalk → ↑ prolactin
• Normal plasma levels: ~5 ng/mL men; ~8 ng/mL women

↑ secretion (stimulants)

• Suckling
• Pregnancy → peak at parturition
• Sleep onset → sustained elevation
• Exercise
• Surgical & psychological stress
• Nipple stimulation
• TRH
• Estrogen (slow direct action on lactotropes)

↓ secretion (inhibitors)

• Dopamine & dopamine agonists (bromocriptine, L-dopa)
• Dopamine receptor blockers (chlorpromazine) → ↑ prolactin

Feedback

• Prolactin ↑ → stimulates dopamine release from median eminence → negative feedback inhibition

Lactation physiology

• After delivery → prolactin returns to baseline in ~8 days
• With prolonged nursing, milk maintained even when prolactin normalizes
• Suckling response magnitude declines after ~3 months

Pituitary Insufficiency

Effects on Endocrine Glands

• Loss of anterior pituitary hormones → predictable multi-gland failure:
• Adrenal cortex atrophies
• ↓ glucocorticoids + ↓ sex steroids
• Stress-induced aldosterone response absent, but basal + salt-depletion aldosterone normal initially
• No early mineralocorticoid deficit → no salt loss/hypovolemia
• Stress intolerance due to ↓ cortisol
• Thyroid hypofunction → ↓ metabolic rate + cold intolerance
• Gonadal atrophy
• Amenorrhea/sexual cycle stops
• Loss of secondary sex characteristics
• Growth failure in children

Insulin Sensitivity + Glucose

• Hypophysectomy → fasting hypoglycemia
• Diabetes symptoms improve
• ↑ response to insulin due to:
• ↓ glucocorticoids AND
• lack of anti-insulin action of growth hormone

→ stronger insulin effect than adrenalectomy alone

Water Metabolism

• Posterior pituitary destruction → diabetes insipidus
• BUT removal of both lobes → only transient polyuria:
• ↓ ACTH → ↓ protein catabolism
• ↓ TSH → ↓ metabolic rate

→ ↓ filtered solute load → ↓ osmotic diuresis

• GH deficiency ↓ GFR + renal plasma flow; GH replacement ↑ both
• Glucocorticoid deficiency → impaired free water excretion
• Former “anterior pituitary diuretic hormone” explained by loss of:
• ACTH, TSH, GH effects

Other Features

• Adult GH deficiency occurs with other pituitary deficiencies
• ↓ ACTH + pituitary peptide hormones with MSH activity → pallor
• Protein loss small; wasting uncommon → patients usually well nourished

Causes of Pituitary Failure

• Pituitary adenomas
• Suprasellar cysts (Rathke pouch remnants)
• Postpartum pituitary infarction = Sheehan syndrome
• Pregnancy → gland enlarged
• Portal system vulnerable in shock
• Infarction extremely rare in men