15 terms
Pituitary Disorder
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Pituitary Hormone Review
Anterior Pituitary (Adenohypophysis):
- Blocked Hypothalamic Regulation = Increase Prolactin / Decrease everything else
1. TSH = Stimulates Thyroid
2. ACTH
3. FSH / LH
4. GH
5. Prolactin
Posterior Pituitary (Neurohypophysis):
1. ADH
2. Oxytocin
Pituitary located in Sella Turcica
- Blocked Hypothalamic Regulation = Increase Prolactin / Decrease everything else
1. TSH = Stimulates Thyroid
2. ACTH
3. FSH / LH
4. GH
5. Prolactin
Posterior Pituitary (Neurohypophysis):
1. ADH
2. Oxytocin
Pituitary located in Sella Turcica
Hormone Deficiencies (Hypopituitarism)
1. Growth Hormone = Short Stature
2. Gonadotropin = Reduced Libido / Amenorrhea
3. ACTH = Loss of Pigmentation / Hypoadrenalism
4. TSH = Hypothyroidism
5. Panhypopituitarism
- Sheehan's Syndrome
6. ADH = Diabetes Insipidus
7. Prolactin = Rare
Causes:
- Destruction / Necrosis
- Ischemia
- Surgery / Radiation
- Inflammation
- Non-functional Pituitary Adenoma (Second Most Common Pituitary Tumor)
2. Gonadotropin = Reduced Libido / Amenorrhea
3. ACTH = Loss of Pigmentation / Hypoadrenalism
4. TSH = Hypothyroidism
5. Panhypopituitarism
- Sheehan's Syndrome
6. ADH = Diabetes Insipidus
7. Prolactin = Rare
Causes:
- Destruction / Necrosis
- Ischemia
- Surgery / Radiation
- Inflammation
- Non-functional Pituitary Adenoma (Second Most Common Pituitary Tumor)
Hormone Excess (Hyperpituitarism)
1. Prolactinoma = Most Common
2. Acromegaly + Gigantism (GH)
3. Cushing's Disease (ACTH)
(Rarely TSH / LH / FSH)
2. Acromegaly + Gigantism (GH)
3. Cushing's Disease (ACTH)
(Rarely TSH / LH / FSH)
Pituitary Enlargement (Mass Effect)
Effects:
1. Bitemporal Hemianopsia (Loss of Peripheral Vision)
- Compression of Optic Chiasm
2. Elevated Intracranial Pressure = Headache / Nausea / Vomit
- Can Hemorrhage = risk of sudden death
Invasion of Hypothalamus:
- Hyperphagia = Central Satiety Center
- Loss of Temp Regulation
MRI = Tumor in Sella Turcica with Bone Destruction
- Can invade Cavernous Sinus / Hypothalamus / 3rd Ventricle / Circle of Willis
1. Bitemporal Hemianopsia (Loss of Peripheral Vision)
- Compression of Optic Chiasm
2. Elevated Intracranial Pressure = Headache / Nausea / Vomit
- Can Hemorrhage = risk of sudden death
Invasion of Hypothalamus:
- Hyperphagia = Central Satiety Center
- Loss of Temp Regulation
MRI = Tumor in Sella Turcica with Bone Destruction
- Can invade Cavernous Sinus / Hypothalamus / 3rd Ventricle / Circle of Willis
Anterior Pituitary Histo
Reticulin Stain = Highlights Acinar Clusters
- Reticulin breaks down due to disorganized Acinar Clusters in Adenoma
- Reticulin breaks down due to disorganized Acinar Clusters in Adenoma
Pituitary Adenomas
Benign Neoplasms of Anterior Pituitary
Pathogenesis:
1. GH Adenoma = G-Protein Mutations (GNAS1)
- Increases cAMP = Hormone Synthesis
2. Mutation of PKA / Cyclin D1 / HRAS / Menin / p27 / KIP1 / AIP / Rb
Microadenomas = <10mm
- Incidental finding in 25% of population
Macroadenomas = >10mm
Pathogenesis:
1. GH Adenoma = G-Protein Mutations (GNAS1)
- Increases cAMP = Hormone Synthesis
2. Mutation of PKA / Cyclin D1 / HRAS / Menin / p27 / KIP1 / AIP / Rb
Microadenomas = <10mm
- Incidental finding in 25% of population
Macroadenomas = >10mm
Multiple Endocrine Neoplasia Syndrome
Type 1 = MEN1 Mutation (Menin Protein)
- Parathyroid Hyperplasia
- Pituitary Adenoma (1/3 of pts)
- Pancreatic Islet Cell Tumor
Type 2 = RET Mutation
- Medullary Thyroid Carcinoma
- Pheochromocytoma
- Type 2A = Parathyroid Hyperplasia (1/3 of pts)
- Type 2B = + Ganglioneuroma
Secretes 2 or more different hormones
- Parathyroid Hyperplasia
- Pituitary Adenoma (1/3 of pts)
- Pancreatic Islet Cell Tumor
Type 2 = RET Mutation
- Medullary Thyroid Carcinoma
- Pheochromocytoma
- Type 2A = Parathyroid Hyperplasia (1/3 of pts)
- Type 2B = + Ganglioneuroma
Secretes 2 or more different hormones
Prolactinoma
Symptoms:
- Milky Discharge from Breast
- Amenorrhea
Causes of High Prolactin:
1. Pregnancy
2. Drugs = Dopamine Antagonists / Antidepressants / H2 Antagonists
- Increased x2
3. Renal Failure
4. Stress = increased x2
5. Tumor compressing Pituitary Stalk = Disconnection
- Increases x2-10
6. Microadenoma = x5
7. Macroadenoma = > x10
Effects of High Prolactin:
- Causes Lactation
- Suppresses GnRH
Histo:
- Composed of Chromophobe Cells
- Prominent Nucleolus
- Endocrine Amyloid + Psammoma Bodies
- Lactotropes = Stain for Prolactinoma
Treatment = Dopamine Agonist (Bromocriptine / Cabergoline)
- Regain normal menstruation in 2 months
- Fertility restored in 6 months
- Milky Discharge from Breast
- Amenorrhea
Causes of High Prolactin:
1. Pregnancy
2. Drugs = Dopamine Antagonists / Antidepressants / H2 Antagonists
- Increased x2
3. Renal Failure
4. Stress = increased x2
5. Tumor compressing Pituitary Stalk = Disconnection
- Increases x2-10
6. Microadenoma = x5
7. Macroadenoma = > x10
Effects of High Prolactin:
- Causes Lactation
- Suppresses GnRH
Histo:
- Composed of Chromophobe Cells
- Prominent Nucleolus
- Endocrine Amyloid + Psammoma Bodies
- Lactotropes = Stain for Prolactinoma
Treatment = Dopamine Agonist (Bromocriptine / Cabergoline)
- Regain normal menstruation in 2 months
- Fertility restored in 6 months
Somatotroph Adenoma (Gigantism + Acromegaly)
Symptoms:
- Increasing Shoe / Ring Size
- Headache / Nausea / Vomit
- Joint Pain / Neuropathy
- Prognathism = Prominent Lower Jaw
- Bitemporal Hemianopsia / Diabetic Retinopathy
- Visceral Organ Growth
Labs:
- Hyperglycemia / Hyperlipidemia
- Hypercalcemia / HTN
- Insulin-like Growth Factor-1 (IGF-1)
- Secondary Diabetes
Histology:
1. Densely Granulated = SLOW growing tumor
- Strongly POS for GH
2. Sparsely Granulated = Fibrous bodies made of Keratin 8
- FAST Growing tumor
Gigantism = in kids / teens
- Crippled by nerve, muscle, joint problems
- Acromegaly develops post-puberty
Acromegaly = Arthritis / Joint Deformities
- Good prognosis with therapy
- Skeletal changes are IRREVERSIBLE
Types:
- Mixed Somatotroph-Lactotroph Adenoma = Secretes GH + PRL from Different Cells
- Mammosomatotroph Adenoma = SAME Cell secretes both GH + PRL
- Acidophil Stem Cell = Aggressive tumor
Treatment:
- Surgery is Preferred
- Octreotide = Somatostatin analogue
- Pegvisomant = GH Antagonist
- Increasing Shoe / Ring Size
- Headache / Nausea / Vomit
- Joint Pain / Neuropathy
- Prognathism = Prominent Lower Jaw
- Bitemporal Hemianopsia / Diabetic Retinopathy
- Visceral Organ Growth
Labs:
- Hyperglycemia / Hyperlipidemia
- Hypercalcemia / HTN
- Insulin-like Growth Factor-1 (IGF-1)
- Secondary Diabetes
Histology:
1. Densely Granulated = SLOW growing tumor
- Strongly POS for GH
2. Sparsely Granulated = Fibrous bodies made of Keratin 8
- FAST Growing tumor
Gigantism = in kids / teens
- Crippled by nerve, muscle, joint problems
- Acromegaly develops post-puberty
Acromegaly = Arthritis / Joint Deformities
- Good prognosis with therapy
- Skeletal changes are IRREVERSIBLE
Types:
- Mixed Somatotroph-Lactotroph Adenoma = Secretes GH + PRL from Different Cells
- Mammosomatotroph Adenoma = SAME Cell secretes both GH + PRL
- Acidophil Stem Cell = Aggressive tumor
Treatment:
- Surgery is Preferred
- Octreotide = Somatostatin analogue
- Pegvisomant = GH Antagonist
Growth Hormone vs IGF-1
Growth Hormone Effects:
- Synergizes with Cortisol
- Antagonizes Insulin
- Increases Lipolysis = Atherosclerosis
- Increases GFR = Water Retention / HTN / Edema
- Increased Thyroxine (T3) = Anxiety / Mental Problems
- Increased Growth of Epiphyseal Bone Plate = Gigantism
- Increased Bone Turnover = Acromegaly
- Synergizes with Cortisol
- Antagonizes Insulin
- Increases Lipolysis = Atherosclerosis
- Increases GFR = Water Retention / HTN / Edema
- Increased Thyroxine (T3) = Anxiety / Mental Problems
- Increased Growth of Epiphyseal Bone Plate = Gigantism
- Increased Bone Turnover = Acromegaly
Hypopituitarism
Loss of 2 or more Anterior Pituitary Hormones
- Usually caused by destruction caused by a tumor (Mass Effect)
- Pituitary Apoplexy = Bleeding into Adenoma
Causes:
- Pituitary Adenoma (Adults)
- Craniopharyngioma (Kids)
- Sheehan Syndrome (Post-Partum)
In Kids = Mental + Growth Retardation
- Symmetrical Dwarfism
- Delayed Puberty
Progression:
1. GH is lost first = Pt doesn't feel good
2. FSH / LH lost = Decreased Libido / Amenorrhea
3. TSH / ACTH lost = Life Threatening
- Usually caused by destruction caused by a tumor (Mass Effect)
- Pituitary Apoplexy = Bleeding into Adenoma
Causes:
- Pituitary Adenoma (Adults)
- Craniopharyngioma (Kids)
- Sheehan Syndrome (Post-Partum)
In Kids = Mental + Growth Retardation
- Symmetrical Dwarfism
- Delayed Puberty
Progression:
1. GH is lost first = Pt doesn't feel good
2. FSH / LH lost = Decreased Libido / Amenorrhea
3. TSH / ACTH lost = Life Threatening
Sheehan Syndrome
(Pan-Hypopituitarism)
(Pan-Hypopituitarism)
Symptoms:
- Lethargy / Weakness
- Hair Loss (Including Pubic Hair)
- Recent Pregnancy / Amenorrhea
- Loss of Weight (GH) / Decreased Libido (FSH/LH)
- Cold Intolerance (TSH)
- Decreased Skin Pigmentation (ACTH)
Pathogenesis:
- Postpartum Necrosis of Ant. Pituitary
- Caused by Postpartum Hypotension
- Reduced blood supply to pituitary which increases in size during pregnancy
- Post. Pituitary spared due to rich blood supply
- Lethargy / Weakness
- Hair Loss (Including Pubic Hair)
- Recent Pregnancy / Amenorrhea
- Loss of Weight (GH) / Decreased Libido (FSH/LH)
- Cold Intolerance (TSH)
- Decreased Skin Pigmentation (ACTH)
Pathogenesis:
- Postpartum Necrosis of Ant. Pituitary
- Caused by Postpartum Hypotension
- Reduced blood supply to pituitary which increases in size during pregnancy
- Post. Pituitary spared due to rich blood supply
Craniopharyngioma
Symptoms:
- Hypopituitarism = Growth Retardation
- Delayed Puberty
- Central Diabetes Insipidus
- Hyperphagia / Obesity
- Loss of Thirst Sensation / Temp Regulation
Diagnosis:
- CT = Supra-Sellar Tumor with CALCIFICATIONS
Histo:
- Keratin Deposits / Calcifications
- Cytokeratin Stain POS
- Cholesterol Crystals = Looks like Clear Rectangle
Pathogenesis (Dual Theory):
1. Metaplastic Theory = Metaplasia of Adenohypophyseal Cells in Ant. Pituitary
- Leads to formation of Tumor forming Squamous Cells
2. Embryogenetic Theory = Remnant of Craniopharyngeal Duct (Epithelium) undergoes neoplastic transformation
Prognosis:
- Locally aggressive / may compress + destroy pituitary
- NOT Malignant (Doesn't Metastasize)
- Hypopituitarism = Growth Retardation
- Delayed Puberty
- Central Diabetes Insipidus
- Hyperphagia / Obesity
- Loss of Thirst Sensation / Temp Regulation
Diagnosis:
- CT = Supra-Sellar Tumor with CALCIFICATIONS
Histo:
- Keratin Deposits / Calcifications
- Cytokeratin Stain POS
- Cholesterol Crystals = Looks like Clear Rectangle
Pathogenesis (Dual Theory):
1. Metaplastic Theory = Metaplasia of Adenohypophyseal Cells in Ant. Pituitary
- Leads to formation of Tumor forming Squamous Cells
2. Embryogenetic Theory = Remnant of Craniopharyngeal Duct (Epithelium) undergoes neoplastic transformation
Prognosis:
- Locally aggressive / may compress + destroy pituitary
- NOT Malignant (Doesn't Metastasize)
Central Diabetes Insipidus
Symptoms:
- Polyuria (5-20L) / Constantly Thirsty
- Decreased ADH
- Hypernatremia (Dehydration)
- Babies = Obese (crying = looks hungry)
Diagnosis:
1. Water Deprivation Test = No changes in Urine Osmolarity
2. ADH (Desmopressin) Administration Test = Normal Urine Osmolarity
[Nephrogenic DI = No change in osmolarity after both tests]
Pathogenesis:
- ADH Deficiency due to lesion somewhere along pathway
- Hypothalamo-Hypophyseal Tract / Axon Terminal / Paraventricular Nucleus / Supraoptic Nucleus
- Inability to produce or release ADH
- Tumors / Trauma / Surgery / Congenital
- If water is restricted = severe dehydration
Nephrogenic Diabetes Insipidus:
- Inability of the kidneys to respond to ADH
- Normal / elevated levels of ADH present
- Polyuria (5-20L) / Constantly Thirsty
- Decreased ADH
- Hypernatremia (Dehydration)
- Babies = Obese (crying = looks hungry)
Diagnosis:
1. Water Deprivation Test = No changes in Urine Osmolarity
2. ADH (Desmopressin) Administration Test = Normal Urine Osmolarity
[Nephrogenic DI = No change in osmolarity after both tests]
Pathogenesis:
- ADH Deficiency due to lesion somewhere along pathway
- Hypothalamo-Hypophyseal Tract / Axon Terminal / Paraventricular Nucleus / Supraoptic Nucleus
- Inability to produce or release ADH
- Tumors / Trauma / Surgery / Congenital
- If water is restricted = severe dehydration
Nephrogenic Diabetes Insipidus:
- Inability of the kidneys to respond to ADH
- Normal / elevated levels of ADH present
SIADH
Caused by Carcinoma in Lung / other organs
- Excessive ADH secreted by Tumor (Ectopic ADH Production)
- Results in severe water retention by kidneys
Clinical Presentation:
- Headache / Vomit
- NO Edema / HTN
Labs:
- Hyponatremia:
115-120 mEq/L = Confusion
< 110 mEq/L = Coma / Seizures
- Decreased Serum Osmolarity
Pathogenesis:
- Water Retention occurs Intracellularly = Cell Expansion
- Excessive ADH secreted by Tumor (Ectopic ADH Production)
- Results in severe water retention by kidneys
Clinical Presentation:
- Headache / Vomit
- NO Edema / HTN
Labs:
- Hyponatremia:
115-120 mEq/L = Confusion
< 110 mEq/L = Coma / Seizures
- Decreased Serum Osmolarity
Pathogenesis:
- Water Retention occurs Intracellularly = Cell Expansion