1
Q
Anterior Pituitary hormones
A
ACTH
LH
FSH
GH
PRL
TSH
2
Q
Which glands are affected with primary, secondary, tertiary deficiencies?
A
Primary - Target gland
Secondary - Pituitary
Tertiary - Hypothalamus
3
Q
Where do most problems occur in the hypothalamus-pituitary axis?
A
Hypothalamus and Pituitary
(Tertiary and Secondary)
4
Q
Posterior pituitary
A
- Consists of neurons with a cell body in the hypothalamus and the axon ending in the posterior pituitary
- Neurons release the small peptides oxytocin and ADH directly into the blood
5
Q
Posterior Pituitary Disorders
A
Hypersecretion of ADH - SIADH
Hyposecretion of ADH - Diabetes Insipidus
Hypersecretion of oxytocin - Galactorrhea
Hyposecretion of oxytocin - lack of milk ejection, prolonged labor, lack of compassion/bonding
6
Q
What are the causes of SIADH?
A
- Ectopic production of ADH (by cancer cells)
- Surgery (surgery related stress)
- Some drugs
- Cranial abnormalities (trauma, tumor, etc)
7
Q
What are the clinical manifestations of SIADH?
A
- ↑water retention
- ↑Na+ loss due to ↑BV
- Hyponatremia - blood is becoming more dilute while urine is becoming more concentrated
- Hypoosmolarity - ↓serum osmolarity
The body is slowlyl becoming hypOtonic; the urine, hypERtonic
8
Q
What are actions of SIADH?
A
- ↑permeability of renal collecting duct to water
- ADH inserts aquaporins into the wall of the collecting duct
- Constriction of arterial SM @ high concentrations
9
Q
What are treatments for SIADH?
A
- Restrict H2O
- Remove tumor (if present)
- ADH receptor blocker
10
Q
What are the clinical manifestations of diabetes insipidus?
A
- Manifests with polyuria (high urine flow)
- Polydipsia - drinking lots of H2O
- Dilute urine - cannot concentrate it
- Dehydration
11
Q
What are the different types of diabetes insipidus?
A
- Neurogenic
- Nephrogenic
- Psychogenic
12
Q
Neurogenic Diabetes Insipidus
A
Insufficient ADH
Damage to the brain or posterior pituitary from head trauma, cranial surgery or tumor; idiopathic
13
Q
Nephrogenic Diabetes Insipidus
A
Insufficient ADH response
- Lack of ADH receptors in kidney or failure of receptors to modify permeability of the collecting duct
- Genetic
- Temporary nephro DI can be caused by some drugs, pregnancy, electrolyte imbalance, kidney trauma
- Permanent nephro DI from kidney failure
14
Q
Psychogenic Diabetes Insipidus
A
Drinking too much H2O
From trying to get rid of toxins, demons?!, etc
15
Q
Tx for Neurogenic DI?
A
ADH replacement
16
Q
Tx for nephrogenic DI?
A
Drink lots of H2O and eat a lot of NaCl
17
Q
Tx for psychogenic DI?
A
Restrict H2O intake
18
Q
What is oxytocin release stimulated by?
A
- Cervix stretching during birth
- Breast stimulation (nursing)
- Psychological: Hearing the baby cry, thinking about the baby, stress
19
Q
What are the effects of oxytocin?
A
- Role in intimacy (bonding, orgasm)
- May cause a degree of amnesia
- Endorphins might also play a role
20
Q
What are the hormones that are released by the anterior pituitary?
A
- FSH - Follicle Stimulating hormone
- LH - Lutenizing hormone
- ACTH - Adrenocorticotrophic hormone
- TSH - Thyroid Stimulating hormone
- PRL - Prolactin
- GH - Growth hormone
21
Q
Hormone pairs in the hypothalamic-pituitary axis
A
- GnRH –> FSH, LH
- TRH –> TSH
- CRH –> ACTH
- PIF –> PRL
- GHRH –> GH
22
Q
Hypothalamic Factor Stimulation Tests
A
Determining if problem originates in hypothalamus or anterior pituitary
- Take blood from patient under resting conditions
- Inject one or more hypothalamic releasing factors
- Wait a few minutes and then take another sample
- Compare the amount of various anterior pituitary hormones before and after injection of hypothalamic factors
If pituitary hormone increases - Hypothalamus
If pituitary hormone does NOT increase - Pituitary
Hypothalamic hormone is high, pituitary hormone is low - Target gland
23
Q
Anterior pituitary disorders
A
Hypopituitarism - Pituitary infarction, Empty sella syndrome
Hyperpituitarism - Pituitary adenoma, end organ destruction, hypothalamic disorder, carcinoma (not as common as adenoma)
24
Q
Tx of pituitary adenoma
A
- Hormone therapies (depending on the problem)
- Surgery (may return)
- Radiation
25
Symptoms of pituitary adenoma
* Visual defect (if tumor is large)
* Headache (if tumor is large)
* Oculomotor palsies may result
* Manifestation: can't properly dilate or constrict the pupil in one or both eyes
* No eye tracking
* Can't open eyelids properly
26
Regulation of PRL Release
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Actions of PRL
* Proliferation of glandular tissue of mammary glands
* Synthesis of milk proteins by mammary glands
* ↑calcium mobilization from bone and secretion of calcium into milk
* Stimulates immune system
28
Sex Effects of Hypersecretion of PRL
* Females
* Amenorrhea
* Galactorrhea
* Hirsutism
* Osteopenia - weakening of the bones due to ↑Ca2+ mobilization
* Males
* Hypogonadism
* Impaired libido
* Infertility
* Gynecomastia
* Galactorrhea
29
Tx for Hypersecretion of PRL
* DA agonists i.e. bromocryptin
* Somatostatin analogs i.e. octreotide
30
Manifestation of Hyposecretion of PRL
* Poor milk production
* Poor immune system function
31
Tx for Hyposecretion of PRL
* ↓plasma concentrations of PRL
* TRH-stimulation test utilized to determine if the problem is at pituitary or hypothalamus
* ↓PRL after TRH injection: problem at pituitary
* ↑PRL release after TRH injection: problem at hypothalamus
32
Hypersecretion of GH disorders
* Gigantism (pre-pubertal adenoma)
* Tall & long limbs
* Acromegaly (post-pubertal adenoma)
* May be tall
* Enlarged bones of face, hands
* Enlarged soft tissues (tongue, heart)
33
Why can GH hypersecretion be lethal?
**Increased risk of hypertrophic cardiomyopathy**
34
What are clinical manifestations of GH hypersecretion?
* Large tongue, lips, fingers, toes, jaw bone, ears, skull bones
* ↑blood glucose
* Headaches if tumor is large
* Vision problems if tumor is large
* Joint pain
* Barrel chest
* CV diseases - HTN, cardiac hypertrophy, etc. = early death
* Malignancies may become more aggressive (GH and IGF are growth factors)
35
Tx for hypersecretion of GH
Somatostatin analog - inhibits GH, glucagon, insulin
36
Hyposecretion of GH
* Growth failure
* ↑% of fat and reduced lean mass
* Poor strength and development of bones (bones are thin and fragile)
* Poor immune function
37
Hyposecretion of GH: young adult onset
* Poor lactation
* Poor immune function
* ↓blood glucose
* Depression
* ↓mass of bone
38
Hyposecretion of GH: GH and aging
* GH falls at about age 60-65
* May cause ↓function of immune system, ↑fat mass, ↓protein mass, ↓bone density associated with aging
* IGF ↑tumor aggressiveness
39
What is the normal regulatory pathway for thyroid hormone?
Hypothalamic TRH \> Pituitary TSH \> T3/T4
40
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43
44
45
46
What are the actions of T3?
* Regulates basal activity of most cells - "Metabolic choke valve"
* Affects cellular activity by binding to an IC receptor and interacting with DNA to ↑mRNA synthesis
* Functions of most cells require thyroid hormones (muscles, nerves, glands, etc)
* ↓thyroid hormones = ↓cell growth, poor protein synthesis, poor conduction of nerve impluses
47
Clinical manifestations of hyerthyroidism AKA thryotoxicosis
* General: weight loss, heat intolerance
* Cardiac: rapid pulse, arrhythmias, clots
* Neuromuscular: tremor
* Skin: warm, moist
* GI: diarrhea
* Eye: exophthalmos, lid lag
* Thyroid storm: extreme, dangerous symptoms
48
What are **common** causes of hyperthyroidism AKA thyrotoxicosis?
* Graves disease
* Multinodular goiter
* Thyroid adenoma
49
What are **uncommon** causes of hyperthyroidism AKA thyrotoxicsis?
* Thyroiditis
* Thyroid carcinoma
* Pituitary adenoma
* Struma ovarii
* Factitious
50
Clinical manifestations of hypothyroidsm AKA myxedema?
* General: fatigue, weight gain, cold intolerance, edema
* Cardiac: slow pulse
* Nervous: delayed reflexes, lethargy
* Skin: rough, dry; hair loss
* Oral: macroglossia
* Myxedema: deepened voice
* Myxedema coma: deteriorating mental status
51
What are **common** causes of hypothyroidism?
* Hashimoto
* Iatrogenic
52
What are **uncommon** causes of hypothyroidism?
* Too little iodine
* 2° hypothyroidism
* 3° hypothyroidism
* Other thyroiditis
53
What are some **non-neoplastic** thyroid disease?
* Thyroiditis
* Graves Disease
* Goiter
54
What diseases fall under **thyroiditis**?
* Hashimoto
* DeQuervain
* Silent
* Reidel
55
What is **Hashimoto**?
Hashimoto - **Autoimmune destruction of thyroid**
* **Most common cause of hypothyroidism in US**
* Females (more susceptible to autoimmune disorders in general)
* **Histological markers: Hurthle cells**
56
What is **DeQuervain**?
DeQuervain - **Immune cross-reaction with thyroid follicles**
* **Enlarged, sore thyroid**
* Follows URI
* Self-limiting
* **Histological markers: Multinucleated giant cell**
57
What is **Silent** Thyroiditis?
Silent - **Cycles of hyper- and hypo-**
* Post-partum or middle age
* Painless, slightly enlarged thyroid
* **Histological markers: Lymphoid infiltrate**
58
What is **Reidel?**
Reidel - **Hard, inflamed mass**
* Hypothyroidism
* Rare
* If large enough, may **compress the trachea**
* **Histological markers: Extensive fibrosis**
59
Graves Disease
Graves Disease
* Most common cause of hyperthyroidism in the US
* **Type II hypersensitivity** - Ab-Ag complex mediated
* Autoimmune: Anti-TSH receptor antibodies stimulate TSH receptors
* TSI activates hormone production and thyroid gland growth so TSH and TRH would be low because they're trying to make them stop producing the thyroid hormone
* Triad of symptoms
* Histological markers: **Hyperplasia of epithelium; scalloped colloid**
60
What is the **Triad of Symptoms** for Graves Disease?
Triad of symptoms:
* General Hyperthyroidism Symptoms
* Exophthalmos
* Dermopathy - abnormal edema (like a unique form of edema); skin texture looks like an orange peel
61
Tx for Graves Disease?
Treatment - controlling symptoms
* Beta blockers (to control symptoms)
* Iodine blockers (thiouracil)
* Hot iodine (radioactive)
* Surgery
62
Goiter
The presence of a goiter only provides evidence that there is some problem with the thyroid axis
Two origins
1. Inflammatory
2. Non-inflammatory (hyperstimulation)
Can be present with:
* ↓thyroid hormones
* ↑thyroid hormones
* Normal thyroid hormones
As TSH levels are high to make more thyroid hormone, but also stimulates growth
--\> Goiter
63
What is T3 and T4?
T3 = Thyroxine
T4 = Triiodothyronine
64
What are **neoplastic** thyroid diseases?
Adenoma
Carcinoma
65
Thyroid Adenoma & Carcinoma - Which is common? Uncommon?
Adenoma - Common
Carcinoma - Uncommon
66
What are the different types of thyroid carcinomas? Rank in order from most common to rarest..
**Most Common**
1. Papillary thyroid carcinoma
2. Follicular thyroid carcinoma
3. Medullary thyroid carcinoma
4. Anaplastic thyroid carcinoma
**Rarest**
67
Papillary Thyroid Carcinoma
Papillary thyroid carcinoma - MOST COMMON
* \>95% 10yr survival
* **Orphan Annie tumor**
* Younger women
* Mild
* Nuclei
* Histological features: **Psamomma body** (Ca2+ rich deposits)
68
Follicular Thyroid Carcinoma
Follicular thyroid carcinoma - SECOND MOST COMMON
* 95% 10yr survival in young patients with small, minimally invasive tumor
* **Prognosis gets worse with ↑age, size, invasiveness**
* Histological features: **Vascular invasion**
69
Medullary Thyroid Carcinoma
Medullary thyroid carcinoma - RARE
* Endocrine tumor (or parafollicular cells)
* **Parafollicular cells** release **calcitonin** (regulates Ca2+ cells)
* 90% 10yr survival if confined to thyroid
* 20% 10 yr survival if metastasized
70
Anaplastic Thyroid Carcinoma
Anaplastic thyroid carcinoma - RAREST TYPE
* Bulky, fast-growing, invasive neck mass
* Pure chaos in the thyroid gland
* Usually **metastatic** at dx
* **BAD** PROGNOSIS - \<10% 5yr survival
71
Parathyroid Glands
* Small glands located behind the upper and lower poles of the thyroid gland
* Produce **parathyroid hormone**
* **Regulate serum Ca2+**
* **Calcitonin antagonist**
72
Alterations of parathyroid function
Hyperparathyroidism
Hypoparathyroidism
73
Types of **hyperparathyroidism**
* **Primary** hyperparathyroidism
* **Excess secretion of PTH from one or more parathyroid glands**
* **Secondary** hyperparathyroidism
* **↑PTH secondary to a chronic disease causing hypocalcemia (i.e. renal failure)**
74
What usually causes **hypoparathyroidism**?
Parathyroid damage during thyroid sugery
75
What are the different layers of the adrenal glands? What hormones are produced by each layer?
* Cortex
* Glomerulosa
* Mineralocorticoids - Aldosterone
* Retain SALT
* Fasciculata
* Glucocorticoids - Cortisol
* Release SUGAR
* Reticularis
* Sex hormones - Androgens, Estrogens
* SEX
* Medulla
* Epi
* NE
76
Cushing Syndrome vs. Cushing Disease
* Cortisol Hypersecretion
* Cushing **Syndrome** - **Elevated plasma cortisol**
* Iatrogenic (taking too much cortisol) - most common
* **_Adrenal tumor_**
* Cushing **Disease** - **Elevated ACTH** production b/c of **_pituitary tumor_**
* W/ subsequent elevated cortisol
77
Tx for **cortisol hypersecretion**
Tx: Remove or destroy the tumor; ↓cortisol injections
78
Clinical manifestations of **cortisol hypersecretion**
Clinical manifestations
* Insulin resistance
* Weight gain (trunk and moon face)
* ↑blood glucose
* Muscle wasting, weakness b/c of muscle breakdown
* AA supporting gluconeogenesis
* Osteoporosis
* ↓inflammatory activity
* Poor wound healing and immune system function
* Thin skin
* **↑sensitivity to catecholamines b/c of ↑adrenergic receptors**
* **↑BP, HR**
* Altered mental status (depression, psychosis, irritability)
79
Sex steroid hypersecretion
* Feminization - estrogens
* Virilzation - androgens
Problem @ reticularis layer?
80
Catecholamine Hypersecretion
Adrenal Medulla Hyperfunction
## Footnote
**Caused by tumors derived from chromaffin cells of the ADRENAL MEDULLA**
**_Pheochromocytoma_**
81
Symptoms of catecholamine hypersecretion
* ↑HR, BP
* Diaphoresis (sweating)
* Weight loss
* Hyperglycemia/hyperlipidemia
82
What are some **adrenal hypotension** syndromes?
Addison Disease (primary adrenal insufficiency)
Waterhouse-Friderichsen Syndrome
83
What is Addision Disease
Primary adrenal insufficiency
* ↓↓cortisol and mineralocorticoids
* Usually autoimmune at origin
84
What are symptoms of **Addison Disease**?
* Slow onset
* Weakness
* Hypotension
* **Skin hyperpigmentation:** oral manifestation - **making too much ACTH because there's no feedback that cortisol levels are low due to adrenal gland deficiency** and when you have a lot of ACTH, you also have a lot of MSH
85
What is **Waterhouse-Friderichsen Syndrome**?
**Hemorrhaging at the adrenal gland caused by**
* Bacterial infection (N. meningitidis)
* Massive, bilateral adrenal hemorrhage
* Hypotension, shock
* **DIC** - disseminated intravascular coagulation
86
What is MEN syndrom and what are the two classifications?
Multiple Endocrine Neoplasia
* Genetic disorder
* Endocrine disorder
* Two classifications:
* MEN-1
* MEN-2
87
What are the features of MEN syndrome?
* Younger people
* Multifocal
* Aggressive
88
What are the features of **MEN-1**?
* **Parathyroid** hyperplasia
* **Pancreatic** hormone tumors
* **Pituitary** adenoma
* **Duodenal** gastrinoma
* Carcinoid (neuroendocrine tumor AKA gut tumor producing 5HT)
* **Thyroid**/adrenal adenomas
* **Lipomas**
89
What are the genetics of **MEN-1**?
**_MEN1_** gene mutation
* Encodes menin
* Tumor suppressor gene
* Mutation turns gene **_off_**
90
What are the features of **MEN-2A & -2B**?
* \*Medullary **thyroid** carcinoma
* **Pheochromocytoma** - produces catecholamines
* **Parathyroid** hyperplasia
91
What are the genetics of **MEN-2A & -2B**?
**_RET_ gene mutation**
* Proto-oncogene
* Encodes tyrosine kinase receptor
* Mutation turns gene **_on_**
92
What is the only difference between **MEN-2A and -2B**?
MEN-2B has a collagen mutation!!!!!
* **Marfanoid habitus**
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DMD 5248
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