Physiology of Anterior Pituitary Hormones¶
Chapter 390 | Part 12: Endocrinology
KEY CLINICAL POINTS¶
- Anterior pituitary hormones (GH, PRL, ACTH, TSH, FSH, LH) are regulated by hypothalamic releasing factors and exhibit pulsatile secretion patterns.
- Prolactin (PRL) suppresses reproductive function and maintains lactation, while GH drives growth and metabolism through IGF-1.
- Feedback loops (e.g., TRH-PRL, GnRH-LH/FSH) and circadian rhythms govern hormone secretion, with disruptions linked to disorders like acromegaly and hypopituitarism.
- Diagnostic testing requires consideration of pulsatility (e.g., 24-h urine cortisol, IGF-1) and context-specific hormonal interactions.
- Dopamine agonists, GH analogs, and targeted therapies are key in managing hyperprolactinemia, acromegaly, and GH deficiency.
1. DEFINITION & OVERVIEW¶
The anterior pituitary, or adenohypophysis, produces six major hormones: GH, PRL, ACTH, TSH, FSH, and LH. These hormones regulate target glands (adrenal, thyroid, gonads) and metabolic processes. Hormone secretion is pulsatile, controlled by hypothalamic releasing factors (e.g., GnRH, TRH) and feedback mechanisms.
Table 390-1 Anterior Pituitary Hormone Expression and Regulation¶
| CELL | CORTICOTROP E | SOMATOTROP E | LACTOTROPE | THYROTROPE | GONADOTROP E |
|---|---|---|---|---|---|
| Tissue-specific transcription factor | T-Pit | Prop-1, Pit-1 | Prop-1, Pit-1 | Prop-1, Pit-1, TEF | SF-1, DAX-1 |
| Developmental timing | 6 weeks | 8 weeks | 12 weeks | 12 weeks | 12 weeks |
| Hormone | POMC | GH | PRL | TSH | FSH, LH |
| Protein | Polypeptide | Polypeptide | Polypeptide | Glycoprotein a, b subunits | Glycoprotein a, b subunits |
| Amino acids | 266 (ACTH 1–39) | 191 | 198 | 211 | 210, 204 |
| Stimulators | CRH, AVP, cytokines | GHRH, ghrelin | Estrogen, TRH, VIP | TRH | GnRH, activins, estrogen |
| CELL | CORTICOTROP E | SOMATOTROP E | LACTOTROPE | THYROTROPE | GONADOTROP E |
|---|---|---|---|---|---|
| Inhibitors | Glucocorticoids | Somatostatin, IGF-1 | Dopamine | T3, T4, dopamine, sex steroids, somatostatin, glucocorticoids | Sex steroids, inhibin |
| Target gland | Adrenal | Liver, bone, other tissues | Breast, other tissues | Thyroid | Ovary, testis |
| Trophic effect | Steroid production | IGF-1 production, growth, insulin antagonism | Milk production | T synthesis and secretion | Sex steroid production, follicle growth, germ cell maturation |
| Normal range | ACTH, 4–22 pg/L | <0.5 mg/La | M <15 mg/L; F <20 mg/L | 0.1–5 mU/L | M, 5–20 IU/L; F (basal), 5–20 IU/L |
1.1 Hormonal Rhythms¶
Hormonal rhythms are entrained to circadian cycles and environmental cues (e.g., light/dark, meals). For example, GH peaks during sleep, while PRL surges during non-REM sleep. Disrupted rhythms (e.g., sleep deprivation) alter metabolic and endocrine function.
1.2 Pulsatile Secretion¶
All anterior pituitary hormones are secreted in pulses. GnRH pulses drive LH/FSH release, while TRH stimulates TSH. Pulsatility is critical for normal function; continuous exposure (e.g., GnRH agonists) causes desensitization.
2. EPIDEMIOLOGY¶
The anterior pituitary weighs ~600 mg and is located in the sella turcica. Developmental anomalies (e.g., Pit-1/Prop-1 mutations) cause selective hormone deficiencies. Hormonal rhythms are age-dependent: GH declines with age, while PRL levels rise during pregnancy/lactation.
2.1 Anatomical Development¶
Pituitary development from Rathke’s pouch involves transcription factors (e.g., Prop-1, Pit-1) and growth factors. Corticotropes express POMC, while somatotropes/ lactotropes share common precursors.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Hormone secretion is regulated by hypothalamic releasing factors (e.g., GnRH, TRH) and feedback loops. Pulsatile release is mediated by GPCRs (e.g., GHRH receptor). Disruptions in these pathways cause disorders like acromegaly (GH excess) or hypopituitarism (deficiency).
3.1 Feedback Mechanisms¶
Negative feedback (e.g., T3/T4 inhibiting TSH) and positive feedback (e.g., estrogen boosting LH during ovulation) modulate hormone release. Dopamine suppresses PRL, while TRH stimulates TSH.
3.2 Pulsatility Regulation¶
GnRH pulses drive LH/FSH secretion; continuous exposure causes desensitization. GH release is influenced by GHS-R agonists, ghrelin, and stress. PRL secretion is inhibited by dopamine and stimulated by estrogen.
4. CLINICAL FEATURES¶
PRL suppresses reproduction and maintains lactation. GH drives growth and metabolism via IGF-1. ACTH stimulates cortisol production, while TSH regulates thyroid function. FSH/LH control gonadal steroidogenesis and gametogenesis.
4.1 Prolactin¶
PRL induces lactation and suppresses GnRH/LH/FSH. Hyperprolactinemia causes infertility, galactorrhea, and hypogonadism. Hypoprolactinemia may result from pituitary tumors or dopamine receptor defects.
4.2 Growth Hormone¶
GH deficiency causes growth retardation in children and sarcopenia in adults. Excess GH (acromegaly) leads to organomegaly, metabolic syndrome, and cardiovascular disease.
5. DIFFERENTIAL DIAGNOSIS¶
Hyperprolactinemia differentiates between pituitary tumors (e.g., prolactinoma) and non-pituitary causes (e.g., hypothyroidism, medications). Acromegaly must be distinguished from other growth hormone excess states (e.g., McCune-Albright syndrome).
5.1 Prolactinoma¶
Prolactinomas are the most common pituitary tumor. Diagnosis requires measuring PRL levels and imaging (MRI).
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnostic tests include serum hormone assays (e.g., IGF-1, TSH), 24-h urine cortisol, and stimulation tests (e.g., TRH for TSH, GnRH for LH/FSH). Pulsatility is assessed via serial measurements or pharmacologic challenges.
6.1 Hormone Assays¶
Normal ranges: PRL (10–25 µ g/L), GH (0.002–0.005 µ g/L), IGF-1 (100–300 ng/mL). Random GH measurements are unreliable; integrated 24-h GH or IGF-1 is preferred.
7. MANAGEMENT & TREATMENT¶
Hyperprolactinemia is treated with dopamine agonists (e.g., cabergoline). Acromegaly uses somatostatin analogs, GH receptor antagonists (pegvisomant), or surgery. GH deficiency is managed with recombinant GH, while hypopituitarism requires hormone replacement.
7.1 Hyperprolactinemia¶
Dopamine agonists (e.g., cabergoline) suppress PRL. Surgery or radiation is reserved for large tumors. Medications (e.g., antipsychotics) may cause hyperprolactinemia.
7.2 Acromegaly¶
Surgery (transsphenoidal) is first-line. Medical therapies include octreotide, lanreotide, and pegvisomant. Radiation is used for residual disease.
8. PROGNOSIS & COMPLICATIONS¶
Untreated GH excess (acromegaly) leads to diabetes, cardiovascular disease, and premature death. Hypopituitarism increases mortality from infections and metabolic complications. Prolonged hyperprolactinemia causes infertility and osteoporosis.
8.1 Acromegaly¶
Early treatment improves outcomes. Complications include arthropathy, hypertension, and tumor risk. IGF-1 levels correlate with disease severity.
9. SPECIAL CONSIDERATIONS¶
Pregnancy increases PRL and suppresses GH. Pediatric GH deficiency requires lifelong treatment. Elderly patients show age-related GH decline, but IGF-1 remains relatively preserved. Hormonal interactions (e.g., estrogen feedback) must be considered in women.
9.1 Pregnancy¶
PRL rises during pregnancy/lactation, while GH levels decline. Prolactinomas may grow during pregnancy, requiring close monitoring.
10. KEY POINTS & CLINICAL PEARLS¶
- Pulsatile hormone secretion is critical for normal function; continuous exposure causes desensitization.
- IGF-1 is the primary mediator of GH’s metabolic effects, with levels reflecting GH status.
- Dopamine agonists are first-line for hyperprolactinemia, while somatostatin analogs treat acromegaly.
- 24-h urine cortisol and IGF-1 are better than single measurements for assessing GH or adrenal function.
- Hormonal interactions (e.g., estrogen feedback) must be considered in differential diagnoses.