ENDOCRINOLOGY
APPROACH TO PATIENT WITH ENDOCRINE DISORDERS Mechanism:
• Receptor defect
I. CORE PRINCIPLES • Post-receptor signaling defect
Endocrinology = Disorders of hormone excess, deficiency, or
resistance IV. CLINICAL EVALUATION – BOARD ESSENTIALS
Fundamental concepts A. History
• Hormone secretion Assess symptoms of excess or deficiency:
• Hormone action via receptors Examples:
• Feedback regulation (mostly negative feedback) Cushing syndrome → central obesity, striae, weakness
Treatment principles Hypothyroidism → fatigue, dry skin, cold intolerance
• Hormone deficiency → Physiologic replacement Hyperthyroidism → weight loss, palpitations
• Hormone excess → Surgery, pharmacologic suppression, or tumor Ask:
removal • Drug history (steroids)
• Hormone resistance → Treat underlying cause or use higher • Family history (MEN syndromes)
hormone levels
Most endocrine disorders are highly treatable if correctly diagnosed B. Physical Examination
Focus on endocrine organs:
II. MAJOR ENDOCRINE ORGANS • Thyroid enlargement or nodules
Classic glands • Testicular size
• Pituitary • Skin changes
• Thyroid • Fat distribution
• Parathyroid
• Adrenal V. LABORATORY EVALUATION – MOST IMPORTANT DIAGNOSTIC
• Pancreatic islets TOOL
• Gonads A. Hormone Measurement Principles
Important non-classic endocrine organs Measured via:
• Brain – hypothalamus • Immunoassay (most common)
• Heart – ANP • Mass spectrometry (most accurate)
• Kidney – renin, erythropoietin Samples:
• GI tract – GLP-1, gastrin, ghrelin • Serum → most hormones
• Adipose tissue – leptin, adiponectin • 24-hour urine → cortisol, metanephrines, calcium
Always consider:
III. PATHOPHYSIOLOGY OF ENDOCRINE DISORDERS • Age
A. Hormone Excess – Causes • Sex
1. Tumors (most common) • Circadian rhythm
• Pituitary adenoma • Medications
• Adrenal adenoma Example:
• Thyroid adenoma Cortisol highest: early morning
2. Autoimmune stimulation Lowest: midnight
• Graves disease → TSH receptor antibodies
3. Exogenous hormone intake VI. BASAL TESTING – KEY BOARD CONCEPT
4. Genetic mutations Use upstream and downstream hormones
• MEN1 – tumor suppressor mutation Examples:
• MEN2 – RET proto-oncogene activation Primary gland failure:
• GPCR mutations → McCune-Albright syndrome Low testosterone + HIGH LH → Primary hypogonadism
Secondary failure:
B. Hormone Deficiency – Causes Low testosterone + LOW LH → Pituitary disease
1. Autoimmune destruction (MOST COMMON) Thyroid evaluation:
• Hashimoto thyroiditis TSH + Free T4
• Type 1 diabetes
• Addison disease VII. DYNAMIC TESTING – EXTREMELY HIGH YIELD
2. Gland destruction Suppression tests → hormone excess
• Surgery Example:
• Tumor Dexamethasone suppression test → Cushing syndrome
• Infection Normal:
• Hemorrhage (Sheehan syndrome) Dexamethasone suppresses cortisol
3. Genetic defects Abnormal:
• Hormone synthesis No suppression → Cushing syndrome
• Receptors
• Enzymes Stimulation tests → hormone deficiency
Example:
C. Hormone Resistance ACTH stimulation test → adrenal insufficiency
Hormone present but ineffective Normal:
Examples: Cortisol increases
• Insulin resistance → Type 2 diabetes Abnormal:
• Androgen resistance → XY female phenotype No cortisol increase
• GH resistance → low IGF-1, high GH
VIII. COMMONLY SCREENED ENDOCRINE DISORDERS
,ENDOCRINOLOGY
Screen high-risk patients for:
• Diabetes mellitus
• Thyroid disease
• Osteoporosis
• Adrenal disorders (selected cases)
,ENDOCRINOLOGY
MECHANISMS OF HORMONE ACTION Examples:
T4/T3 → TBG
I. HORMONE CLASSES – VERY HIGH YIELD TABLE Cortisol → CBG
Hormone class Receptor Examples Testosterone → SHBG
IMPORTANT:
Peptides Membrane Insulin, GH, PTH Only FREE hormone is active
Catecholamines Membrane Epinephrine
Steroids Nuclear Cortisol, estrogen V. HORMONE HALF-LIFE – BOARD RELEVANCE
Short half-life:
Thyroid hormone Nuclear T3, T4
ACTH, PTH, GH
Vitamin D Nuclear Calcitriol Long half-life:
KEY RULE: T4 = 7 days
• Lipid-soluble → Nuclear receptor T3 = 1 day
• Water-soluble → Membrane receptor Clinical implication:
T4 takes weeks to reach steady state
II. MEMBRANE RECEPTORS – HIGH YIELD
1. GPCR (Most common) VI. FEEDBACK REGULATION – MOST IMPORTANT CONCEPT
Mechanism: Negative feedback (MOST COMMON)
Hormone → GPCR → cAMP or IP3/DAG Examples:
Examples: T3/T4 ↓ TSH
• TSH Cortisol ↓ ACTH
• ACTH Testosterone ↓ LH
• LH, FSH
• PTH Positive feedback (RARE)
• Glucagon Example:
Diseases: Estrogen ↑ → LH surge → ovulation
Activating mutation → hyperfunction
Inactivating mutation → hypofunction VII. HORMONAL RHYTHMS – VERY HIGH YIELD
Example: Circadian rhythm
McCune-Albright syndrome Cortisol highest → morning
Lowest → midnight
2. Tyrosine Kinase Receptors Important test:
Examples: Midnight cortisol → Cushing syndrome
• Insulin
• IGF-1 Pulsatile secretion
Mechanism: GH, LH, GnRH
Receptor autophosphorylation Loss of pulsatility → endocrine dysfunction
Disease:
Insulin receptor mutation → severe insulin resistance VIII. HORMONE SYNTHESIS DIFFERENCES – BOARD FAVORITE
Peptide hormones:
3. Cytokine receptors Stored in vesicles
Examples: Released rapidly
• GH Examples:
• Prolactin Insulin, ACTH
Mechanism: Steroid hormones:
JAK-STAT pathway Not stored
Disease: Synthesized on demand
GH receptor defect → Laron dwarfism Examples:
Cortisol, testosterone
4. Serine kinase receptors
Examples: PSBIM PEARLS – TOP 20 BOARD MUST-REMEMBER
• TGF-β 1. Most endocrine disorders = hormone excess or deficiency
• Activin 2. TSH + Free T4 = best initial thyroid test
Signal via SMAD proteins 3. Dexamethasone suppression test = Cushing diagnosis
4. ACTH stimulation test = adrenal insufficiency
III. NUCLEAR RECEPTORS – EXTREMELY HIGH YIELD 5. Primary gland failure → high tropic hormone
Examples: 6. Secondary gland failure → low tropic hormone
• Cortisol 7. Only FREE hormone is biologically active
• Thyroid hormone 8. Steroid hormones act on nuclear receptors
• Vitamin D 9. Peptide hormones act on membrane receptors
• Estrogen 10. Insulin uses tyrosine kinase receptor
• Testosterone 11. GH uses JAK-STAT receptor
Mechanism: 12. GPCR = most common receptor type
Hormone enters cell → binds receptor → regulates gene transcription 13. Negative feedback regulates most endocrine axes
Slow onset, long duration 14. Cortisol highest in morning
15. Graves disease = antibody stimulation of TSH receptor
IV. HORMONE TRANSPORT – VERY HIGH YIELD 16. MEN syndromes = tumor-related hormone excess
Many hormones circulate bound to proteins: 17. Hormone resistance = hormone present but ineffective
, ENDOCRINOLOGY
18. T4 has long half-life → slow treatment adjustment
19. Dynamic testing distinguishes deficiency vs excess
20. Correct diagnosis → endocrine diseases are highly treatable
APPROACH TO PATIENT WITH ENDOCRINE DISORDERS Mechanism:
• Receptor defect
I. CORE PRINCIPLES • Post-receptor signaling defect
Endocrinology = Disorders of hormone excess, deficiency, or
resistance IV. CLINICAL EVALUATION – BOARD ESSENTIALS
Fundamental concepts A. History
• Hormone secretion Assess symptoms of excess or deficiency:
• Hormone action via receptors Examples:
• Feedback regulation (mostly negative feedback) Cushing syndrome → central obesity, striae, weakness
Treatment principles Hypothyroidism → fatigue, dry skin, cold intolerance
• Hormone deficiency → Physiologic replacement Hyperthyroidism → weight loss, palpitations
• Hormone excess → Surgery, pharmacologic suppression, or tumor Ask:
removal • Drug history (steroids)
• Hormone resistance → Treat underlying cause or use higher • Family history (MEN syndromes)
hormone levels
Most endocrine disorders are highly treatable if correctly diagnosed B. Physical Examination
Focus on endocrine organs:
II. MAJOR ENDOCRINE ORGANS • Thyroid enlargement or nodules
Classic glands • Testicular size
• Pituitary • Skin changes
• Thyroid • Fat distribution
• Parathyroid
• Adrenal V. LABORATORY EVALUATION – MOST IMPORTANT DIAGNOSTIC
• Pancreatic islets TOOL
• Gonads A. Hormone Measurement Principles
Important non-classic endocrine organs Measured via:
• Brain – hypothalamus • Immunoassay (most common)
• Heart – ANP • Mass spectrometry (most accurate)
• Kidney – renin, erythropoietin Samples:
• GI tract – GLP-1, gastrin, ghrelin • Serum → most hormones
• Adipose tissue – leptin, adiponectin • 24-hour urine → cortisol, metanephrines, calcium
Always consider:
III. PATHOPHYSIOLOGY OF ENDOCRINE DISORDERS • Age
A. Hormone Excess – Causes • Sex
1. Tumors (most common) • Circadian rhythm
• Pituitary adenoma • Medications
• Adrenal adenoma Example:
• Thyroid adenoma Cortisol highest: early morning
2. Autoimmune stimulation Lowest: midnight
• Graves disease → TSH receptor antibodies
3. Exogenous hormone intake VI. BASAL TESTING – KEY BOARD CONCEPT
4. Genetic mutations Use upstream and downstream hormones
• MEN1 – tumor suppressor mutation Examples:
• MEN2 – RET proto-oncogene activation Primary gland failure:
• GPCR mutations → McCune-Albright syndrome Low testosterone + HIGH LH → Primary hypogonadism
Secondary failure:
B. Hormone Deficiency – Causes Low testosterone + LOW LH → Pituitary disease
1. Autoimmune destruction (MOST COMMON) Thyroid evaluation:
• Hashimoto thyroiditis TSH + Free T4
• Type 1 diabetes
• Addison disease VII. DYNAMIC TESTING – EXTREMELY HIGH YIELD
2. Gland destruction Suppression tests → hormone excess
• Surgery Example:
• Tumor Dexamethasone suppression test → Cushing syndrome
• Infection Normal:
• Hemorrhage (Sheehan syndrome) Dexamethasone suppresses cortisol
3. Genetic defects Abnormal:
• Hormone synthesis No suppression → Cushing syndrome
• Receptors
• Enzymes Stimulation tests → hormone deficiency
Example:
C. Hormone Resistance ACTH stimulation test → adrenal insufficiency
Hormone present but ineffective Normal:
Examples: Cortisol increases
• Insulin resistance → Type 2 diabetes Abnormal:
• Androgen resistance → XY female phenotype No cortisol increase
• GH resistance → low IGF-1, high GH
VIII. COMMONLY SCREENED ENDOCRINE DISORDERS
,ENDOCRINOLOGY
Screen high-risk patients for:
• Diabetes mellitus
• Thyroid disease
• Osteoporosis
• Adrenal disorders (selected cases)
,ENDOCRINOLOGY
MECHANISMS OF HORMONE ACTION Examples:
T4/T3 → TBG
I. HORMONE CLASSES – VERY HIGH YIELD TABLE Cortisol → CBG
Hormone class Receptor Examples Testosterone → SHBG
IMPORTANT:
Peptides Membrane Insulin, GH, PTH Only FREE hormone is active
Catecholamines Membrane Epinephrine
Steroids Nuclear Cortisol, estrogen V. HORMONE HALF-LIFE – BOARD RELEVANCE
Short half-life:
Thyroid hormone Nuclear T3, T4
ACTH, PTH, GH
Vitamin D Nuclear Calcitriol Long half-life:
KEY RULE: T4 = 7 days
• Lipid-soluble → Nuclear receptor T3 = 1 day
• Water-soluble → Membrane receptor Clinical implication:
T4 takes weeks to reach steady state
II. MEMBRANE RECEPTORS – HIGH YIELD
1. GPCR (Most common) VI. FEEDBACK REGULATION – MOST IMPORTANT CONCEPT
Mechanism: Negative feedback (MOST COMMON)
Hormone → GPCR → cAMP or IP3/DAG Examples:
Examples: T3/T4 ↓ TSH
• TSH Cortisol ↓ ACTH
• ACTH Testosterone ↓ LH
• LH, FSH
• PTH Positive feedback (RARE)
• Glucagon Example:
Diseases: Estrogen ↑ → LH surge → ovulation
Activating mutation → hyperfunction
Inactivating mutation → hypofunction VII. HORMONAL RHYTHMS – VERY HIGH YIELD
Example: Circadian rhythm
McCune-Albright syndrome Cortisol highest → morning
Lowest → midnight
2. Tyrosine Kinase Receptors Important test:
Examples: Midnight cortisol → Cushing syndrome
• Insulin
• IGF-1 Pulsatile secretion
Mechanism: GH, LH, GnRH
Receptor autophosphorylation Loss of pulsatility → endocrine dysfunction
Disease:
Insulin receptor mutation → severe insulin resistance VIII. HORMONE SYNTHESIS DIFFERENCES – BOARD FAVORITE
Peptide hormones:
3. Cytokine receptors Stored in vesicles
Examples: Released rapidly
• GH Examples:
• Prolactin Insulin, ACTH
Mechanism: Steroid hormones:
JAK-STAT pathway Not stored
Disease: Synthesized on demand
GH receptor defect → Laron dwarfism Examples:
Cortisol, testosterone
4. Serine kinase receptors
Examples: PSBIM PEARLS – TOP 20 BOARD MUST-REMEMBER
• TGF-β 1. Most endocrine disorders = hormone excess or deficiency
• Activin 2. TSH + Free T4 = best initial thyroid test
Signal via SMAD proteins 3. Dexamethasone suppression test = Cushing diagnosis
4. ACTH stimulation test = adrenal insufficiency
III. NUCLEAR RECEPTORS – EXTREMELY HIGH YIELD 5. Primary gland failure → high tropic hormone
Examples: 6. Secondary gland failure → low tropic hormone
• Cortisol 7. Only FREE hormone is biologically active
• Thyroid hormone 8. Steroid hormones act on nuclear receptors
• Vitamin D 9. Peptide hormones act on membrane receptors
• Estrogen 10. Insulin uses tyrosine kinase receptor
• Testosterone 11. GH uses JAK-STAT receptor
Mechanism: 12. GPCR = most common receptor type
Hormone enters cell → binds receptor → regulates gene transcription 13. Negative feedback regulates most endocrine axes
Slow onset, long duration 14. Cortisol highest in morning
15. Graves disease = antibody stimulation of TSH receptor
IV. HORMONE TRANSPORT – VERY HIGH YIELD 16. MEN syndromes = tumor-related hormone excess
Many hormones circulate bound to proteins: 17. Hormone resistance = hormone present but ineffective
, ENDOCRINOLOGY
18. T4 has long half-life → slow treatment adjustment
19. Dynamic testing distinguishes deficiency vs excess
20. Correct diagnosis → endocrine diseases are highly treatable
