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Questions and Answers
Which of the following is NOT a macro priority in the management of Diabetes Mellitus?
Albuminuria is one of the macro priorities for managing Diabetes Mellitus.
True
Name one treatment priority for patients with Diabetes Mellitus who do not have kidney disease.
Blood Pressure
The macro priorities for Diabetes Mellitus management include Heart Failure, ASCVD, and __________.
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Match the following management priorities with their descriptions:
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Which type of pituitary adenoma is defined as being greater than 1 cm?
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Functioning adenomas do not cause hormonal dysfunction.
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What is one potential effect of a non-functioning adenoma related to the stalk effect?
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A pituitary adenoma smaller than 1 cm is called a _________.
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Match the following effects with their related adenoma type:
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Which of the following hormones is released from magnocellular neurons in the hypothalamus?
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The anterior pituitary is influenced solely by releasing hormones from the hypothalamus.
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What is the role of the hypothalamic-hypophysial portal system?
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The hormone _____ is stored in the posterior pituitary and is involved in the regulation of water balance.
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Match the following hormones with their corresponding actions:
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What is the most common type of pituitary adenoma associated with increased prolactin levels?
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Macro-prolactin is the bioactive form of prolactin.
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What type of pathway does prolactin act through?
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The primary inhibitor of prolactin secretion is ______.
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Match the following substances with their role in prolactin regulation:
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What is the female to male ratio for microprolactinoma?
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Macroprolactinoma has a higher prevalence in males compared to females.
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What age range is most commonly affected by prolactinoma?
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The female to male ratio for macroprolactinoma is __________.
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Match the following types of prolactinoma with their respective female to male ratios:
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What is the first-line medical treatment for symptomatic macroadenoma?
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Bromocriptine is the preferred medication during pregnancy.
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What is the maximum dose increase for cabergoline in the management of symptomatic macroadenoma?
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The last resort for treating resistant prolactinoma when surgery is not an option is _____ therapy.
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Match the treatment options to their indications or notes:
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What is a likely cause of prolactin levels greater than 200 µg/L?
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Macroprolactin is always symptomatic.
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Name one physiological condition that can cause prolactin levels to rise.
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Prolactin levels between 40-100 µg/L can be indicative of __________ and systemic conditions.
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Match the prolactin level ranges with their associated conditions:
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Which structure is located posteriorly to the pituitary gland?
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The internal carotid artery is in lateral relation to the pituitary gland.
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What is the diagnostic sign of Central Diabetes Insipidus observed on a T1 MRI?
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A pituitary adenoma that is smaller than 1 cm is called a __________.
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Match the MRI type with its description:
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What is the primary origin of the anterior pituitary?
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The posterior pituitary develops from upgrowth from the oral ectoderm.
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What is the most important mutation associated with congenital hypopituitarism?
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Congenital hypopituitarism frequently results from pituitary __________.
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Match the following features with their related conditions:
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Which type of cell is the earliest to appear in the anterior pituitary?
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The Somatotrophs make up 50% of the cells in the anterior pituitary.
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What hormone does the Gonadotrophs produce?
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Corticotrophs secrete __________, which is a precursor for several hormones.
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Match the following hormones with their respective cell types:
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At what week do Lactotrophs appear?
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FSH and LH are produced by the Lactotrophs.
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What transcription factor mutation is associated with congenital hypopituitarism?
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Study Notes
Pituitary Adenoma
- Pituitary adenomas are tumors of the pituitary gland.
-
Types:
- Macroadenoma: > 1 cm
- Microadenoma: < 1 cm
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Non-functioning Adenoma:
- Stalk effect: leads to hypopituitarism and prolactinoma.
- Mass effect: leads to intracranial tension
-
Functioning Adenoma:
- Leads to hormonal dysfunction
Hypothalamus & Pituitary Gland
-
Hypothalamus relation with anterior pituitary:
- Hypothalamic influence over hormones:
- Positive: CRH, TRH, GNRH, GHRH (Some inhibitory effect of somatostatin)
- Negative: Prolactin (By prolactin inhibitory factor PRIF - Dopamine)
- Hypothalamic influence over hormones:
-
Hypothalamus relation with posterior pituitary:
- Supraoptic and paraventricular neurons in Hypothalamus
- Magnocellular neurons produce oxytocin
- Pro vasopressin travels to posterior pituitary neurons
- Cleaves into Neurophysin and Copeptin
- ADH stored in posterior pituitary
- Supraoptic and paraventricular neurons in Hypothalamus
Prolactin
-
Constituent:
- Polypeptide of 199 amino acids
- Forms microprolactin (little prolactin) 23KD: Bioactive form
- Macro-prolactin: inactive form assessed by gel filtration chromatography
- Similar to Growth Hormone (GH): produced from lateral part of pituitary gland by lactotroph cells
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Function:
- Acts via JAK/STAT pathway
- Induces and maintains lactation in an already primed breast (Estrogen + Progesterone)
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Stimulators:
- Estrogen
- TRH
- VIP
- Oxytocin
- REM sleep
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Inhibitors:
- PRIF (Prolactin Inhibitory Factor)/Dopamine via tubulo-infundibular pathway
Prolactinoma
-
Causes:
- α-subunit of FSH secreting adenoma (most common), clinically insignificant
- Prolactinoma (most common): microadenoma
- GH secreting adenoma (most common): Acromegaly (macro-adenoma)
- ACTH secreting adenoma (third most common): Cushing's disease (micro > macro)
Prolactinoma Treatment
-
Asymptomatic microadenoma: Wait and watch (3-6 months)
- Repeat MRI if size increases → Then treat
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Symptomatic/macroadenoma:
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Medical (first line): Dopamine agonists
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Cabergoline (DOC):
- A/E: Nausea, vomiting, postural hypotension, dizziness
- ↑ ½ weekly dosing
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Bromocriptine:
- Used in pregnancy
- Higher incidence of adverse events
- Stop 7 days before lactation
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Cabergoline (DOC):
-
Surgery:
- Indications: Dopamine agonist resistance, persistent visual field defects after 1 month of medical Rx, unstable pituitary apoplexy, pregnancy; unresponsive to short course medical therapy
- Radiotherapy (Gamma Knife stereotactic radiotherapy): Last resort (if patient unfit for surgery)
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Medical (first line): Dopamine agonists
Prolactinoma Prevalence
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Sex:
- Microprolactinoma: Female to Male ratio is 20:1
- Macroprolactinoma: Female to Male ratio is 1:1 (men present late)
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Age:
- 25-45 years (most common)
Hyperprolactinemia
-
Causes:
-
Drugs:
- Da Blockers: Conventional antipsychotics
- Metoclopramide: Atypical antipsychotic
- Opiates
- Verapamil
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Drugs:
Fasting Prolactin Levels
Prolactin levels (µg/L) | Associated Conditions |
---|---|
< 25 | |
25-40 | Physiological: Sleep, stress, Pregnancy (variable, up to 180 µg/L), Lactation, Chest wall stimulation. |
40-100 | Drugs, systemic conditions. |
> 100 | Adenoma (↑ probability) |
> 200 | Definite adenoma (Rule out macroprolactin) |
Macroprolactin vs Hook Effect
Macroprolactin | Hook effect |
---|---|
↑ Prolactin levels | ↑ Prolactin level |
Asymptomatic | Tumor size not corresponding to prolactin levels |
Anterior Pituitary Cells
Cell Type | Percentage (%) | Appearance (weeks) |
---|---|---|
Somatotrophs | 50% | 12 |
Lactotrophs | 15% | 12-24 |
Thyrotrophs | 5% | 12 |
Gonadotrophs | 10% | 12 |
Corticotrophs | 15% | 6 |
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Characteristics of each cell type:*
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Somatotrophs: Appear by 12 weeks
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Lactotrophs: Last cell to appear, between 12 and 24 weeks
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Thyrotrophs: Appear by 12 weeks
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Gonadotrophs: Appear by 12 weeks. Includes FSH and LH cells
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Corticotrophs: Earliest cells to appear at 6 weeks; located in the center of the gland, and are basophilic.
Pituitary Gland Hormones
Hormone | Description |
---|---|
GH (Growth Hormone) | Polypeptide hormone, 191 AA |
PRL (Prolactin) | Polypeptide hormone, 199 AA |
TSH (Thyroid-Stimulating Hormone) | Appears in the Thyroid Gland |
ACTH (Adrenocorticotropic Hormone) | Stimulates the release of corticosteroids |
FSH (Follicle-Stimulating Hormone) | Part of Gonadotropin, involved in sex hormone production |
LH (Luteinizing Hormone) | Part of Gonadotropin, involved in sex hormone production |
Further Pituitary Gland Information
- 20% of thyroid hormone produced by gland itself
- Acidophilic cell: Located in the lateral portion of the gland. Vulnerable to ischemia. Includes GH-secreting adenomas, also expressing lactotrophs (20% of cases).
- Hyperpigmentation: Associated with pigmentation, possible link to MSH receptors.
- Corticotrophs: Largest granules (400-550nm), secrete POMC (Pro-opio-melanocortin).
- Basophilic: Located in the center of the gland.
Transcription Factors
- Prop-1 mutation → congenital hypopituitarism
- Pit-1 mutations and most common cause hypopituitarism
- Tpit: Corticotroph development
- GATA-2 → SF-1 → DAX-1 → Gonadotrophins
Pituitary Gland Anatomy
- The master gland of endocrine.
Embryology
- Anterior Pituitary: Origin: upgrowth from roof of oral ectoderm. Rathke's pouch (Surface).
- Posterior Pituitary: Origin: Downgrowth from floor of 3rd ventricle (Neurohypophysis).
Applied Aspect
- Congenital Hypopituitarism: most common cause Pituitary dysplasia.
- Transcription factor defect: Prop-1 mutation (most important)
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Anterior Pituitary only involved:
- Midline craniofacial anomaly:
- Rathke's pouch (Nasopharynx)
- Cells from defect in midline migration
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Outcomes (defects in development):
- Single central incisors
- Bifid uvula
- Cleft lip
- Midline craniofacial anomaly:
Pituitary Gland Relations
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Posterior Relation: Sphenoid Sinus
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Lateral Relation: Cavernous sinus
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Ventral Relation: Diaphragma sellae (Duramater layer), Injury CSF leak, Empty sella syndrome
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Structures in relation to pituitary gland:*
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Pituitary stalk
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Diaphragma sellae
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Internal carotid artery
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Oculomotor nerve (III)
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Trochlear nerve (IV)
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Abducent nerve (VI)
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Ophthalmic division of trigeminal nerve (V1)
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Maxillary division of trigeminal nerve (V2)
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Compressed pituitary gland
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Pituitary adenomas: Transsphenoidal approach
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Tumor Expansion: VI nerve involvement (first Lateral rectus palsy)
MRI Imaging of Pituitary Gland
MRI Type | Description |
---|---|
T1 MRI (Coronal image) | Isointense Pituitary |
T1 Sagital MRI | Isointense pituitary |
T1 MRI (without contrast) | Isointense Pituitary |
T1 MRI (with contrast) | Uniform uptake of contrast by Pituitary gland; In Adenoma: Tumor will not take contrast (Less vascularity) not uniform uptake by contrast. |
T1 MRI (Sagittal section) | Normal bright spot of pituitary gland under red circle; Absence of bright spot: Diagnostic of Central DI (80% cases) |
Pituitary Gland Features
- Weight: 600 mg
- Pregnancy: > 1 gm (enlarges)
- Blood loss (PPH): ↓ Blood supply to Gland
- Sheehan Syndrome:
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Description
This quiz explores the types and effects of pituitary adenomas, as well as the relationship between the hypothalamus and the pituitary gland. Understand the dynamics of functioning and non-functioning adenomas, and their hormonal implications. Test your knowledge on these important concepts in neuroendocrinology.