ENDOC- PITUITARY intro and Anterior pituitary Flashcards
1
Q
◦The hypothalamic neural cells synthesize specific releasing and inhibiting hormones that are secreted directly to the pituitary stalk
A
Hypothalamus
2
Q
Pituitary gland is regulated by 3 interacting elements
A
- ◦Hypothalamic inputs
- ◦Feedback effect of circulating hormones
- ◦Paracrine and autocrine secretions of the pituitary itself
3
Q
A
4
Q
-
“master gland” because, together with the hypothalamus, it orchestrates the complex regulator functions of the many endocrine glands
*
A
pituitary gland
5
Q
What is the weight and size of pituitary?
A
The pituitary gland weighs ~600mg (400-900 mg) and measures 13mm x 6-9mm x 9mm
6
Q
Where is the pituitary gland located?
A
Located within the sella turcica ventral to the diaphragma sella
Anatomically and functionally consists of two lobes: the anterior and posterior lobes
7
Q
Anterior pituitary:
◦5 distinct hormone secreting cell types with 6 major hormones
A
- coticotroph cells- secretes POMC and thus ACTH/cortictropin
- Somatotroph cells: expresses growth hormone or somatotropin
- Thyrotroph cells express the common glycoprotein alpha subunit and the specific B subunit of TSH/thyrotropin
- Gonadotroph cells: express the alpha and B subunit of FSH and LH
- Lactotroph cells express prolactin
8
Q
coticotroph cells- secretes _______________
A
POMC and thus ACTH/cortictropin
9
Q
Somatotroph cells: expresses________________
A
growth hormone or somatotropin
10
Q
Thyrotroph cells express the common glycoprotein alpha subunit and the specific B subunit of TSH/thyrotropin
A
common glycoprotein alpha subunit and the specific B subunit of TSH/thyrotropin
11
Q
Gonadotroph cells: express the _______________
A
alpha and B subunit of FSH and LH
12
Q
Lactotroph cells express prolactin
A
prolactin
13
Q
The p____________ is a collection of axon terminals and is directly innervated by hypothalamic neurons via the stalk
A
osterior lobe (neural lobe)
14
Q
3 general pituitary gland dysfunction
A
- Hormone deficiency
- Hormone excess
- Masses- hypothalamic, pituitary and other sellar masses (which can also cause hormone excess or deficiency)
15
Q
Results from impaired production of one or more of the anterior pituitary trophic hormones
- inherited disorders such as pituitary dysplasias/aplasia, congenital CNS mass, transcription factor deficits, etc.
- Acquired disorders due to compressive mass effects, or vascular/inflammatory damage
A
HORMONE DEFICIENCIES
16
Q
HORMONE DEFICIENCIES: Developmental and Genetic Causes
A
1.Pituitary dysplasia
2.Septo-optic dysplasia
◦3.Tissue specific factor mutation
- Kallman Syndrome
- Bardet Biedl Syndrome
- Leptin and Leptin Receptor Mutation
- Prader Willi Syndrome
17
Q
Pituitary dysplasia – aplastic, hypopasltic, ectopic
A
aplastic,
hypopasltic,
ectopic
18
Q
◦Result from dysgenesis of the septum pellucidum or corpus callosum
A
Septo-optic dysplasia
19
Q
◦Several pituitary cell-specific transcription factors such as Pit-1 and Prop-1 are critical for determining the development and committed function of differentiated anterior pituitary cell lineages
A
Tissue specific factor mutation
20
Q
Tissue specific factor mutation
◦Several pituitary cell-specific transcription factors such as_______ and ________ are critical for determining the development and committed function of differentiated anterior pituitary cell lineages
A
Pit-1 and Prop-1
21
Q
Kallman Syndrome
- *◦Defective GnRH synthesis** and is associated with anosmia/hyposmia due to olfactory bulb agenesis/hypoplasia
- *◦Prevents progression through puberty**
A
Kallman Syndrome
22
Q
◦MR, renal abnormalities, obesity, hexa/brady/syndactyly and retinal degeneartion
A
Bardet Biedl Syndrome
23
Q
Leptin and Leptin Receptor Mutation
◦Hyperphagia, obesity adn central hypogonadism
A
Leptin and Leptin Receptor Mutation
24
Q
HORMONE DEFICIENCIES: Developmental and Genetic Causes
Hypogonadotropic hypogonadism, hyperphagia-obesity, adult onset DM, hypotonia, mental retardation
A
Prader Willi Syndrome
25
HORMONE DEFICIENCIES: **Acquired Hypo**pituitarism
* May be caused by **surgical trauma, vascular trauma, pituitary or hypothalamic neoplasms**, **inflammatory disease, infiltrative disorders or irradiation**
* Trophic hormone failure occurs spontaneously:**GH\>FSH\>LH\>TSH/ACTH**
26
HORMONE DEFICIENCIES: Laboratory Investigation
* Biochemical diagnosis of pituitary insufficiency is made by **demonstrating low levels of trophic hormones** in the setting of **low levels of target hormones**
* **Provocative tests** may be **required to assess pituitary reserve**
27
HORMONE DEFICIENCIES: Treatment
**Hormone replacement therapy** with **a treatment regimen** that **mimic physiologic hormone production** allow for maintenance of satisfactory clinical homeostasis
28
Results from **overproduction of one or more of the anterior pituitary trophic hormones** which **can be due to overproduction of** r**eleasing hormones** from the **hypothalamus** or an ectopic source, increase in pituitary cell type, increased sensitivity of the end organ.
**HORMONE EXCESS**
29
HYPOTHALAMIC, PITUITARY AND OTHER SELLAR MASSES
* **Pituitary adenomas**
* **Craniopharyngiomas**
* Rathke’s cysts (\<5mm cysts)
* Sellar chrodomas
* Meningiomas
* Histiocytosis X
* Pituitary Metstasis
* Hypothalamic hamartomas, gangliocytomas
* Hypothalamic and optic gliomas
* Brain germ cell tumors
30
Most common cause of pituitary hormon**e hypo or hypersecretion in adults**
**◦Benign neoplasms** that **arise from one of the 5 anterior cell types**
Pituitary adenomas
31
◦Benign, **suprasellar, cystic masses** that ar**e derived from the Rathke’s pouch and arise near the pituitary stalk**
Craniopharyngiomas
32
HYPOTHALAMIC, PITUITARY AND OTHER SELLAR MASSES
Evaluation
1. Local Mass Effect
2. MRI
3. Ophthalmologic Evaluation
4. Laboratory Investigations
5. Histologic Evaluation
33
HYPOTHALAMIC, PITUITARY AND OTHER SELLAR MASSES
Treatment:
1.Surgery
Transphenoidal vs transcranial surgery
2.Radiation Therapy
3.Medical Therapy
34
6 Major Anterior Pituitary Gland Hormones
1. Prolactin (PRL)
2. Growth Hormone (GH)
3. Adrenocorticotropic Hormone (ACTH)
4. Luteinizing Hormone (LH)
5. Follicle Stimulating Hormone (FSH)
6. Thyrotropin Stimulating Hormone (TSH)
35
PROLACTIN
Synthesized in
lactotroph cells
36
What type of secretion is Prolactin?
Pulsatile secretion
37
What is the normal value of Prolactin?
10-25 ug/L
38
What is the half- life of prolactin?
Half-life of 50 minutes
39
What is the Predominant central control of PRL?
** inhibitory** via the **dopamine-mediated inhibitory effect**
40
Other hormones controlling prolactin release:
**◦Stimulatory**: _______ and \_\_\_\_\_\_\_\_\_\_
1. TRH and
2. VIP
41
Other hormones controlling prolactin release:
**◦Inhibitory: **
* thyroid hormones
* and glucocorticoids
42
When does PRL transiently increases?
* after exercise,
* meals,
* sexual intercourse,
* minor surgical procedures,
* general anesthesia,
* chest wall, injury,
* MI,
* acute stress
43
What are the function of PRL?
* Proliferation of the breast lobuloalveolar epithelium
* Induces and maintain lactation
* Decrease reproductive function and reduce sexual drive
44
PROLACTIN
Decrease reproductive function and reduce sexual drive through:
* suppression of the hypothalamic GnRH
* and suppression of the pituitary gonadotropin secretion
* and impairs gonadal steroidogenesis in both men and women.
45
**Most common pituitary hypersecretion** in **both men and women**
HYPERPROLACTENEMIA
46
What are the physiologic cause of Hyperprolactenemia?
Physiologic causes:
## Footnote
**pregnancy and lactation**
47
What are the pathologic cause of Hyperprolactenemia?
Pathologic causes
* : pituitary hypersecretion,
* hypothalamic-pituitary stalk damage,
* systemic causes (e.g. renal failure, cirrhosis, hypothyroidism)
48
What is the **pharmacologic cause ** of Hyperprolactenemia?
Pharmacologic Causes: **dopamine antagonists**
49
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ are the most common cause of prolactin elevations \>200ug/L
Prolactinomas
50
HYPERPROLACTENEMIA
◦Manifestations:
in women
In women:
* amenorrhea,
* galactorrhea,
* **infertility are the hallmarks,**
* others are **decreased bone mineral density**,
* **decreased libido**,
* **weight gain** and **mild hirsutism**
51
Hyperprolactenemia manifestation in men:
In men:
* **diminished libido,**
* infertility and **visual loss**,
* others are **osteopenia,**
* reduced muscle mass and
* **reduced beard growth**
52
What is the laboratory investigation of Hyperprolactenemia?
Laboratory investigation:
**morning, basal prolactin** and i**nvestigation for other etiologies**
53
: pituitary adenomas
**\<10mm**;
**F:M :: 20:1**
Microprolactinoma
54
: pituitary adenoma
\>10mm;
F:M::1:1
Macroprolactinom
55
What is the treatment for PROLACTINOMA
Treatment:
primarily medical management with **dopamine receptor agonists** (e.g**. Bromocriptine and cabergoline**);
surgical approach or **radiotx** is for invasive prolactinomas or dopamine resistant tumors
56
Most abundant anterior pituitary hormone
GROWTH HORMONE
57
The **hypothalamic peptide \_\_\_\_\_\_\_\_\_\_\_\_\_-stimulates synthesis and secretion of GH**
**GHRH**
58
\_\_\_\_\_\_\_\_\_\_\_\_inhhibits GH release
Somatostatin (SRIF)
59
\_\_\_\_\_\_\_\_\_\_\_\_-produced in the liver, **is the peripheral target hormone for GH** and is the **predominant hormone exerting GH action;**
IGF-1,
60
What type of secretion is GH?
GH secretion is **pulsatile,**
61
The highest levels of GH correlating with the \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
with highest levels correlating with the **onset of *_slow wave_* sleep**
62
What are the metaboloc action of GH
Metabolic action:
* ◦**Induces protein synthesis** and **nitrogen retention**
* **◦Impairs glucose toleramce by antagonizing insulin action**
* **◦Stimulates lipolysis**, leading to **increased circulating fatty acid levels**, **reduced omental fat malls**
* **◦Enhance lean body mass**
* ◦Stimulates **epiphyseal prech**ondrocyte differentiation and **linear bone growth**
63
Short Stature in Children
May be caused by
* ◦GH deficiency
* ◦GHRH receptor mutations
* ◦GH insensitivity
* ◦Nutritional short stature
* ◦Psychosocial short stature
64
Adult GH Deficiency
Clinical feature **include changes in body composition**, **lipid metabolism**, **cardiovascular dysfunction** an**d quality of life**
rare
65
What is the cause of Acromegaly/ gigantism?
Usually the **result of a somatotrope adenoma** but may r**arely be caused by extrapituitary lesion**
66
In Acromegaly, what are the rare GH secretion?
Rare causes of ectopic GH secretion by:
* tumors of pancreas, ovarian, lung, or hematopoietic origin
* while others present with **GHRH-mediated acromegaly such as in chest or abdominal carcinoid tumor.**
67
What is the presentation of Acromegaly/Gigantism?
* **◦Indolent** and **often not clinically diagnosed**
* ◦**Acral bony overgrowth** with **frontal bossing,** **increased hand and foot size, mandibular enlargement with** **prognathism, widened teeth spaces**
* ◦**Soft tissue swelling** with **increased heel pad thickness,** i**ncreased glove and shoe size, ring tightening, coarse facial features, large fleshy nose**
* **◦Hyperhidrosis**, **deep and hollow sounding voice, oily skin, arthropathy, kyphoss,** carpal tunnel syndrome, **proximal muscle weakness and fatigue**, **acanthosis nigricans, skin tags**
68
What are other presentation of Acromegaly/ Gigantism?
Generalized visceromegaly:
* cardiomegaly,
* macroglossia,
* goiter,
* polyps,
* upper airway obstruction
69
What laboratory investigation should be done to diagnose Acromegaly?
Laboratory Investigation:
* *◦Age and sex matched serum IGF-1 levels**
* *◦GH suppression test**
70
What are the treatment goals for Acromegaly/ Gigantism?
* Control **GH and IGF-1** hypersecretion**: somatotropin**, **pegvisomant**, **dopamine agonists**
* ◦**Ablate or arrest tumor growth**: surgery, radiotherapy, stereotactic ablation
* ◦**Ameliorate comorbidities**
* ◦**Restore mortality rates to normal**
* **◦Preserve pituitary function**
71
ADRENOCORTICOTROPIC HORMONE
Stimulated by\_\_\_\_\_\_\_\_\_\_\_\_\_in the hypothalamus
corticotropin releasing hormone (CRH)
72
What type of secretion is ACTH?
ACTH secretion is **pulsatil**e and **exhibits a circadian rhythm** which **peaks at 6 am** and reaches a **nadir at about midnight**
73
When does ACTH peak?
6am
74
When is the lowest point ( nadir) of ACTH?
about mignight
75
What cause an increase in ACTH?
ACTH is also increased by:
* physical and
* psychologic stress,
* exercise,
* acute illness
* and insulin-induced hypoglycemia
76
What is the major function of ACTH?
Major function is to **maintain metabolic homeostasis** and **mediate the neuroendocrine stress** **respons**e through i**nduction of adrenocortical steroidogenesis**
77
What is the characteristic of ACTH deficiency?
Pituitary ACTH deficiency (aka secondary adrenal insufficiency) is characterized by:
* fatigue,
* weakness,
* anorexia,
* nausea,
* vomiting and
* occasional hypoglycemia
78
In **contrast to primary adrenal insufficiency**, **secondary adrenal insufficiency is not accompanied** by\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
hyperpigmentation or mineralocorticoid deficiency
79
How is ACTH deficiency be investigated?
Laboratory investigation:
◦**Inappropriately low levels of ACTH** in the **setting of low cortisol**
80
What is the treatment for ACTH deficiency?
Treatment: Glucocorticoid replacement
81
What is cushing syndrome?
It is caused by prolonged exposure to **elevated levels of either _endogenous glucocorticoids or exogenous glucocorticoids_**
82
ACTH-producing pituitary adenoma
Cushing’s Disease
83
What accounts for 70% of patients with **endogenous Cushing's Syndrome?**
Cushing’s Disease (ACTH-producing pituitary adenoma)
84
What is the typical features of CUshing Disease?
* thin skin,
* central obesity,
* hypertension,
* plethora,
* moon facies,
* purle striae,
* easy bruisability,
* glucose intolerance,
* gonadal dysfunction,
* osteoporosis,
* proximal muscle weakness,
* signs of hyperandrogenism
* and psychological disturbance
85
How will you investigate Cushing's Disease?
Laboratory Investigations:
* ◦24 hour urine free cortisol
* ◦1mg **dexamethasone suppression test**
* ◦Midnight salivary cortisol
* ◦Basal ACTH
86
How will you treat Cushing's Disease?
Treatment:
◦Selective transphenoidal resection
◦Medical Managment: ketoconazole, mitotane
87
What is the function of Gonadotropins: FSH and LH?
Evokes germ cell development and maturation and steroid hormone biosynthesis
88
\_\_\_\_\_\_\_\_\_\_ stimulates the synthesis and secretion of both FSH and LH through its pulsatility
GnRH
89
90
Gonadotropin Deficiency presentation is:
* oligo-amenorhhrea,
* infertility,
* decreased vaginal secretions,
* decreased libido,
* testicular/breart atrophy
91
What treatment Gonadotropin Deficiency?
Treatment**: gonadotropin injections**, **testosterone replaement, OCPs**
92
Note: **most non functioning pituitary adenoma** are ________________ in origin
gonadotrope cells
93
acts to stimulate **thyroid hormone synthesis and release**
THYROTROPIN STIMULATING HORMONE
TSH
94
The\_\_\_\_\_\_\_\_\_\_\_\_\_stimulates TSH synthesis and secretion
hypothalamic TRH
95
What is the difference of TSH deficiency and TSH adenomas in symptom presentation?
**TSH deficiency** shows **symptoms of hypothyroidism** while **TSH adenomas usually present with goiter and hyperthyroidism**
96
TSH deficiency shows symptoms of \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
hypothyroidism
97
**TSH adenoma**s usually present with \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_-
goiter and hyperthyroidism
98
