---

PITUITARY GLAND AND THYROID GLAND

Pharmacy Assignment | Endocrine Pharmacology

---

PART I: THE PITUITARY GLAND

---

1. Anatomy and Structure

• Acidophils (eosinophilic cytoplasm) — produce GH and Prolactin
• Basophils (basophilic cytoplasm) — produce TSH, ACTH, FSH, LH
• Chromophobes (poorly staining) — resting or non-secretory cells

---

2. Hormones of the Anterior Pituitary

Key point for pharmacy: Most hypothalamic factors are stimulatory, but somatostatin and dopamine are inhibitory. Drugs that mimic or block these factors are used clinically. — Robbins, Cotran & Kumar Pathologic Basis of Disease

---

3. Hormones of the Posterior Pituitary

• Synthesized in the supraoptic and paraventricular nuclei of the hypothalamus
• Released in response to increased plasma osmolality (detected by osmoreceptors) or decreased blood volume (detected by baroreceptors in carotid arteries and cardiac atria)
• Acts on renal collecting ducts (V2 receptors) to increase water reabsorption → concentrates urine
• Acts on vascular smooth muscle (V1 receptors) → vasoconstriction
• Pharmacological relevance: Desmopressin (synthetic ADH analogue) is used to treat central diabetes insipidus and bedwetting (enuresis)

• Synthesized in the paraventricular nucleus of the hypothalamus
• Released on nipple stimulation (lactation) and cervical dilation (parturition)
• Actions: stimulates uterine smooth muscle contraction; facilitates milk ejection from mammary ducts
• Pharmacological relevance: Synthetic oxytocin (Pitocin®) is given to induce or augment labor; oxytocin antagonists (e.g., atosiban) are used as tocolytics to prevent preterm labor

---

4. Pituitary Diseases and Their Pharmacological Management

4.1 Hyperprolactinemia (Prolactinoma)

"The ergot-based DA agonists bromocriptine and cabergoline are used in the treatment of hyperprolactinemia. Both have a high affinity for D2 receptors... both activate D2 receptors in the pituitary to reduce prolactin secretion." — Goodman & Gilman's The Pharmacological Basis of Therapeutics

---

4.2 Acromegaly / Gigantism (Excess GH)

---

4.3 Cushing's Disease (Excess ACTH from Pituitary)

• Surgery (transsphenoidal) — first-line
• Pasireotide — somatostatin analogue with activity at SSTR5; reduces ACTH secretion
• Ketoconazole, Metyrapone, Osilodrostat — adrenal steroidogenesis inhibitors (reduce cortisol production)
• Mifepristone — glucocorticoid receptor antagonist

---

4.4 Pituitary Hypofunction (Hypopituitarism)

• GH deficiency → Somatropin (recombinant human GH)
• TSH deficiency → Levothyroxine
• ACTH deficiency → Hydrocortisone or prednisolone
• Gonadotropin deficiency → sex steroids (estrogen/testosterone) or gonadotropin injections (for fertility)
• ADH deficiency (cranial DI) → Desmopressin (DDAVP)

---

5. Summary Table: Key Drugs Acting on the Pituitary Axis

---

---

PART II: THE THYROID GLAND

---

1. Anatomy and Structure

• Divided into lobules by fibrous septa; each lobule contains 20–40 follicles
• Follicles: spherical units lined by cuboidal-to-low-columnar follicular epithelial cells; filled with colloid (thyroglobulin)
• Parafollicular (C) cells: secrete calcitonin, which inhibits osteoclast activity and promotes calcium absorption into bone

— Robbins, Cotran & Kumar Pathologic Basis of Disease

---

2. Thyroid Hormone Biosynthesis

1. Iodide uptake — dietary iodide (I⁻) is actively transported into follicular cells by the sodium/iodide symporter (NIS) on the basolateral membrane
   • Blocked by: perchlorate (ClO₄⁻), thiocyanate (SCN⁻), pertechnetate (TcO₄⁻)
2. Iodide transport to colloid — iodide exits the apical membrane via pendrin (SLC26A4 transporter)
   • Pendred syndrome: pendrin deficiency → goiter + sensorineural deafness
3. Oxidation of iodide to iodine — catalyzed by thyroid peroxidase (TPO) using H₂O₂
   • Blocked by: thioamide drugs (methimazole, propylthiouracil), high intrathyroidal iodide (Wolff-Chaikoff effect)
4. Organification — iodine is attached to tyrosine residues within thyroglobulin → forming monoiodotyrosine (MIT) and diiodotyrosine (DIT) — also catalyzed by TPO
5. Coupling — MIT + DIT → T3 (triiodothyronine); DIT + DIT → T4 (thyroxine) — also by TPO
6. Storage — thyroglobulin (with T3 and T4 attached) is stored as colloid
7. Secretion — on TSH stimulation, colloid is endocytosed, thyroglobulin is proteolyzed → T3 and T4 released into the blood

— Katzung's Basic and Clinical Pharmacology

---

3. Thyroid Hormone Transport and Peripheral Conversion

• Thyroxine-binding globulin (TBG) — major carrier (~70%)
• Transthyretin (prealbumin)
• Albumin

• Most T4 (prohormone) is deiodinated in peripheral tissues (liver, kidney, brain) to the active T3 by deiodinases
• T3 has 10-fold greater receptor-binding affinity than T4
• An inactive form, reverse T3 (rT3), is produced by an alternate deiodination pathway

— Katzung's Basic and Clinical Pharmacology

---

4. Mechanism of Action of Thyroid Hormones

• Basal Metabolic Rate (BMR): ↑ oxygen consumption, ↑ thermogenesis
• Cardiovascular: ↑ heart rate, ↑ contractility, ↑ cardiac output; ↑ expression of beta-1 adrenergic receptors
• CNS: critical for brain development in fetus and neonate; deficiency → irreversible intellectual disability (cretinism)
• Lipid metabolism: ↑ catabolism of cholesterol, ↓ serum cholesterol
• Growth and development: essential for normal linear growth and skeletal maturation
• Protein synthesis: stimulated at physiological levels
• Carbohydrate metabolism: ↑ intestinal glucose absorption, ↑ glycogenolysis

---

5. Hypothalamic-Pituitary-Thyroid (HPT) Axis

Hypothalamus → TRH
       ↓
Anterior Pituitary → TSH
       ↓
Thyroid Gland → T3 + T4
       ↓ (negative feedback)
T3/T4 inhibit both TRH and TSH secretion

• Thyroid growth (hypertrophy and hyperplasia)
• Hormone synthesis and secretion

---

6. Thyroid Function Tests (TFTs)

---

7. Disorders of the Thyroid Gland

7.1 Hyperthyroidism (Thyrotoxicosis)

1. Graves' disease (~85% of cases) — autoimmune; TSH-receptor stimulating antibodies (TRAb) cause unregulated thyroid stimulation
2. Toxic multinodular goiter — autonomous nodules secrete excess hormone
3. Toxic adenoma — single hyperfunctioning nodule

• Tachycardia, palpitations, atrial fibrillation, widened pulse pressure
• Weight loss despite increased appetite
• Heat intolerance, sweating, warm moist skin
• Tremor, anxiety, insomnia, irritability
• Goiter, exophthalmos (in Graves' disease)
• In severe cases: thyroid storm (life-threatening)

---

7.2 Drugs Used in Hyperthyroidism

"Both decrease the synthesis of T4 and may enhance remission by reducing TSH receptor antibody concentrations (the primary pathologic mechanism in Graves disease). Propylthiouracil also decreases the conversion of T4 to the more potent T3." — Miller's Anesthesia

---

• Perchlorate (ClO₄⁻), Thiocyanate, Pertechnetate — competitively block NIS → prevent iodide uptake
• Rarely used clinically; risk of aplastic anemia with perchlorate

---

• High-dose iodide paradoxically inhibits thyroid hormone synthesis and release — the Wolff-Chaikoff effect
• Used preoperatively before thyroidectomy to reduce vascularity of the gland
• Controls symptoms within 7–10 days
• Effect is transient (gland eventually "escapes" inhibition)
• Also used in thyroid storm as adjunct therapy

---

• Taken up by thyroid follicular cells via NIS
• Emits beta radiation → destroys thyroid tissue
• Leads to permanent hypothyroidism requiring lifelong levothyroxine
• Contraindicated in pregnancy and breastfeeding
• Most commonly used definitive treatment in adults with Graves' disease

---

• Propranolol — drug of choice; blocks sympathetic symptoms (tachycardia, tremor, anxiety); also inhibits peripheral T4→T3 conversion at high doses
• Atenolol, Metoprolol — cardioselective alternatives
• Do NOT reduce thyroid hormone levels; used while waiting for antithyroid drugs to take effect or before thyroidectomy

---

7.3 Hypothyroidism

• Fatigue, lethargy, cold intolerance, weight gain
• Bradycardia, constipation, dry skin, hair loss
• Myxedema (non-pitting edema from glycosaminoglycan accumulation)
• Delayed tendon reflexes
• Elevated serum cholesterol
• In infants: cretinism — irreversible intellectual disability, growth failure
• Severe: myxedema coma (life-threatening)

---

7.4 Treatment of Hypothyroidism — Thyroid Hormone Replacement

• Synthetic T4; converted to active T3 in peripheral tissues
• Oral bioavailability: 70–80% (higher with liquid/gel cap formulations)
• Half-life: ~7 days → once-daily dosing
• Average adult dose: 1.7 mcg/kg/day; infants require higher per-kg doses (10–15 mcg/kg/day)
• Monitor TSH 4–6 weeks after dose change; TSH lags behind free T4

• Synthetic T3; nearly complete oral absorption (95%)
• Faster onset; shorter half-life (~1 day) → multiple daily doses needed
• Used when rapid thyroid hormone effect is needed (e.g., myxedema coma — IV formulation)
• Generally NOT preferred over levothyroxine for routine hypothyroidism

---

7.5 Graves' Disease — Special Pharmacological Focus

• Exophthalmos (Graves' ophthalmopathy) — not resolved by antithyroid treatment; treated with glucocorticoids or orbital decompression
• Pretibial myxedema — localized skin infiltration
• Neonatal thyrotoxicosis — maternal TRAb can cross the placenta

1. Antithyroid drugs (methimazole preferred in adults, PTU in first trimester) — 30–50% remission rate after 12–18 months
2. Radioactive iodine (¹³¹I) — most common definitive treatment in adults
3. Surgery (thyroidectomy) — when goiter is very large, malignancy suspected, or in pregnancy (second trimester)

---

7.6 Thyroid Storm (Thyrotoxic Crisis)

1. PTU 500–1000 mg loading dose → blocks new hormone synthesis AND peripheral T4→T3 conversion
2. Lugol's iodide — given 1 hour AFTER PTU to block hormone release (Wolff-Chaikoff effect); giving iodide first would provide substrate for new hormone synthesis
3. Propranolol — controls tachycardia and peripheral T4→T3 conversion
4. Hydrocortisone — reduces peripheral conversion; treats relative adrenal insufficiency
5. Supportive: antipyretics (paracetamol, NOT aspirin — aspirin displaces T4 from TBG), IV fluids, cooling

---

8. Additional Thyroid Drugs

---

PART III: COMPARISON SUMMARY

---

REVIEW QUESTIONS

1. A patient with a prolactinoma is prescribed cabergoline. What is the mechanism of action of this drug, and why is it preferred over bromocriptine?
2. Explain the Wolff-Chaikoff effect. How is this phenomenon exploited pharmacologically in the management of thyroid storm?
3. A pregnant woman in her first trimester is diagnosed with Graves' disease. Which antithyroid drug would you choose and why? What would change in the second trimester?
4. Outline the steps of thyroid hormone biosynthesis and identify at least three pharmacological agents that block different steps of this pathway.
5. A patient on levothyroxine is also taking calcium carbonate three times daily and omeprazole. Her TSH is 24.9 μU/mL (elevated). Explain the drug interactions contributing to her subtherapeutic response.
6. Differentiate between Graves' disease and Hashimoto's thyroiditis in terms of pathophysiology, thyroid function, and treatment.
7. What is the rationale for using propranolol — rather than a cardioselective beta-blocker — in the management of thyrotoxicosis?
8. Explain the mechanism by which somatostatin analogues (e.g., octreotide) are used in the treatment of acromegaly.

---

REFERENCES

• Robbins, Cotran & Kumar. Pathologic Basis of Disease, Chapter 24: The Endocrine System.
• Goodman & Gilman's. The Pharmacological Basis of Therapeutics, Chapter 38: Thyroid and Antithyroid Drugs; Chapter 15: Dopaminergic Agents.
• Katzung's. Basic and Clinical Pharmacology, 16th Edition, Chapter 38: Thyroid & Antithyroid Drugs.
• Miller's Anesthesia, 10th Edition — Preoperative Thyroid Management.

---

• Anatomy (anterior vs posterior lobe, histology, cell types)
• All 6 anterior pituitary hormones + their hypothalamic regulators (table)
• Posterior pituitary hormones: ADH and Oxytocin (with drug applications)
• 4 major pituitary diseases with full pharmacological management:
  • Hyperprolactinemia → Cabergoline, Bromocriptine (mechanism explained)
  • Acromegaly → Octreotide, Pegvisomant, surgery
  • Cushing's disease → Pasireotide, Ketoconazole, Metyrapone
  • Hypopituitarism → replacement therapy for each axis
• Master drug table (8 drugs)

• Anatomy, embryology, histology (follicles, C cells)
• Step-by-step thyroid hormone biosynthesis with drug targets at each step
• Transport proteins, peripheral T4→T3 conversion
• Drug interaction table (TBG modifiers, enzyme inducers)
• HPT axis diagram
• Thyroid function tests reference table
• Hyperthyroidism: causes, clinical features, all drug classes (thioamides, iodide, ¹³¹I, beta-blockers) with detailed MOA
• Hypothyroidism: causes, clinical features, levothyroxine pharmacokinetics, drug interactions
• Graves' disease focus, thyroid storm step-by-step management