Term
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Definition
• An area of the posterior forebrain in the floor and lateral walls of the third ventricle
• Located below the thalamus and above the pituitary
• Comprises approximately 1% of the mass of the brain
• Contains multiple nuclei
• It is the link between nervous system and endocrine system
• Responds to various stimuli including visual, olfactory, stress, blood-borne signals
• Responsible for regulating pituitary function via various stimulatory and inhibitory neuro-hormones |
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Term
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Definition
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Term
| Hormones secreted by hypothalamus |
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Definition
• Anti-diuretic hormone (ADH)
• Corticotropin-releasing hormone (CRH)
• Gonadotropin-releasing hormone (GnRH)
• Growth Hormone-releasing hormone (GHRH) • Somatostatin (-)
• Oxytocin
• Prolactin-releasing hormone (PRH)
• Dopamine (-)
• Thyrotropin-releasing hormone (TRH) |
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Term
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Definition
| Pituitary is in the sella turcica connected to the hypothalamus by the pituitary stalk and venous plexus. |
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Definition
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Definition
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Term
| Posterior Pituitary hormones |
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Definition
• ADH -> stored in posterior pituitary -> Na/H2 balance
• Oxytocin -> stored in posterior pituitary -> milk let down |
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Term
| Anterior Pituitary hormones |
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Definition
• CRH+ -> ACTH -> Cortisol (Adrenals)
• TRH+ -> TSH -> Thyroid Hormone (Thyroid)
• TRH + -> Prolactin -> Milk Synthesis ( Breast)
• GnRH+ -> FSH/LH -> Sex Hormones (Gonads) • GHRH + -> GH -> IGF-1 (liver) -> Growth
• GHRH+ -> Prolactin -> Milk Synthesis (Breast) • Dopamine inhibits -> Prolactin
• Somatostatin inhibits GH and TSH |
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Term
Hypothalamus- Pituitary-End Hormone Pathology Terminology
• When there is an abnormality of a hormone: |
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Definition
• If it is a problem with a PRIMARY organ (IE thyroid, gonads, adrenals) - PRIMARY DISEASE
• If it is a problem with a PITUITARY hormone - SECONDARY DISEASE
• If it is a problem with a HYPOTHALAMIC hormone - TERTIARY DISEASE |
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Term
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Definition
In the pituitary, there are various different tumors that can form and obviously have various effects based on if they're hormone-producing or not hormone-producing. I'll refer to these as we go forward. But just to let you know the incidence of these different tumors, most of your pituitary tumors are going to be in this lactotroph category, so 40% to 50% of pituitary tumors. And those tumors are prolactin-secreting. So those patients are going to have very, very high levels of prolactin.
The second most common pituitary tumor are these clinically nonfunctioning tumors here, 15% to 40%. And those usually present more with hormonal deficits, because we think of it as they're taking up space and preventing the pituitary from secreting hormones.
And then just going in order, then we have our growth hormone-secreting tumors. So those patients will have what we call acromegaly or gigantism. And that's 10% to 20% of the tumors.
The corticotroph, or ACTH-secreting, tumors are 10% to 15% of the tumors. And they give you Cushing's disease. And then the thyrotroph tumors are only 1%. That's TSH-screening tumors. Very rare-- I've never seen any of those before. |
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Term
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Definition
• CNS triggers/ metabolic, physical, mental stress/
diurnal rhythm + CRH -> + ACTH
• ACTH then stimulates synthesis and secretion of corticosteroids ie CORTISOL by the ADRENAL GLANDS
• Cortisol is a steroid hormone that has an effect on multiple tissues
- Increased blood pressure • Increased blood glucose • Alters immune response |
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Term
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Definition
| Here is a visual of the HPA axis, so hypothalamic-pituitary-adrenal axis. As you see, we have our triggers to the hypothalamus, which then stimulates the anterior pituitary to release ACTH, which then stimulates the adrenal gland to secrete cortisol. And then cortisol feeds back in a negatory fashion to both the anterior pituitary and the hypothalamus to say, "OK, we've had enough," to maintain homeostasis throughout the body. |
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Term
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Definition
Cushings
So disorders of the HPA axis-- in any axis, we have deficits and excess. So we'll go over excess cortisol symptoms now. So symptoms of high cortisol include this picture of a human here.
You get a lot of central obesity; Buffalo hump, which is a fatty pad right on the dorsum of the neck; red, round face. Women can get increased hirsutism or facial hair. Women and men can both have acne. There's decreased muscle mass in the proximal limbs. So a lot of these patients can't even get up from a seated position in a chair without using their arms.
It can cause hypotension. It can cause high blood glucose. It can cause increased risks of clots, fatigue, severe depression, menstrual irregularities, and water retention. So not fun.
[image] |
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Definition
[image]
Symptoms of low cortisol-- so a deficit would be fatigue, lack of energy or stamina, reduced strength. A lot of times they have very low blood pressure. So getting up from a seated position, they'll get very dizzy. A lot of these patients have a low-grade nausea throughout the day. They lose weight. A lot of joint pain, generalized muscle pain. So also not fun. |
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Term
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Definition
• ACTH secreting tumor in the pituitary (cushings disease)
• Ectopic ACTH syndrome
- Small cell carcinomas of the lung
- Neuroendocrine tumors of lung, pancreas, thymus.
• Ectopic secretion of CRH (very rare) • Primary adrenal failure |
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Term
| Diagnosis of High ACTH States |
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Definition
-Confirm Hypercortisolemia
• 24 hour urinary free cortisol
• Overnight low dose dexamethasone suppression (1mg)
• Late-night salivary cortisol
-Pituitary tumor vs. Ectopic ACTH secretion
• High- dose dexamethasone suppression test
• 8 mg of dexamethasone taken at 10-11 pm night before labs
• Labs drawn at 7-8 am morning after
• Serum cortisol <5 mcg/dL = PITUITARY SOURCE
- High AM ACTH and CORTISOL • CRH Stimulation test
- Synthetic CRH or corticorelin given to patient
• Increased ACTH and Cortisol = PITUITARY SOURCE
• Absent rise in ACTH = ectopic source
• Once you determine the source, do imaging of suspected site |
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Term
| High ACTH States Treatment |
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Definition
- Pituitary Tumors
• Surgical Removal
• There are medical treatment options available as well for non-surgical candidates
- Ectopic Tumors
• Chemotherapy, Surgery
- Adrenal Insufficiency
• Replacement steroids |
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Term
| High ACTH and LOW AM CORTISOL |
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Definition
| • Most likely primary adrenal failure |
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Term
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Definition
• Pituitary tumor diminishing the secretion of ACTH • Other disorders/injuries leading to hypopituitarism
- TBI
- Autoimmune
- Genetic causes
• Ectopic corticosteroid usage
• Drugs suppressing ACTH
- Opioids
• Adrenal adenoma secreting cortisol
• CRH insufficiency |
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Term
| primary vs secondary adrenal failure |
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Definition
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Term
Diagnosis of Low ACTH States
• Low ACTH and Low Cortisol |
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Definition
- Rule out medication induced
- Differentiate between secondary and tertiary
• CRH stimulation test:
• Administer CRH
• If ACTH levels increase - the deficiency is in the hypothalamus (tertiary)
• If ACTH levels do not increase - deficiency is in the pituitary (secondary) |
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Term
Diagnosis of Low ACTH States
• Low ACTH, high CORTISOL |
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Definition
• Primary Hypercortisolism
• Treatment - remove the source and replace steroid if needed |
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Term
| Treatment - Low ACTH/Low Cortisol |
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Definition
Replace corticosteroid
• Hydrocortisone 15-20 mg qam and 5-10 mg qpm
• Prednisone 5-7.5 mg daily
• Monitor BP
• Monitor subjective symptoms
- Fatigue, dizziness, nausea
• If coming from pituitary or hypothalamus sodium and potassium should not be affected |
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Term
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Definition
- TRH -> + TSH -> + stimulates synthesis and secretion of THYROID HORMONE by the THYROID
- Thyroid Hormone - effects multiple bodily functions • Cardiovascular system
• Nervous system
• Respiratory system
• MSK system
• Gastrointestinal system • Metabolism |
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Term
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Definition
| Here is a picture of the HPT axis, so hypothalamic-pituitary-thyroid axis. So just like the HPA, you have TRH stimulating TSH, which then stimulates the thyroid gland to secrete T3 and T4, which then feed back to the pituitary and the hypothalamus to maintain harmony. |
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Term
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Definition
• Primary hypothyroidism
• Secondary/Central hyperthyroidism - TSH producing adenoma (very rare) |
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Term
| Hyperthyroidism vs Hypothyroidism |
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Definition
There are vastly different symptoms for hypo- and hyperthyroidism. So a lot of this diagnosing can be done on your initial interview with a patient and seeing what kind of symptoms they're experiencing. So a hypothyroid patient is typically going to be cold all the time. They're going to be complaining of weight gain. They're going to be complaining of dry skin, hair loss, brittle nails, constipation.
Hyperthyroid patients are going to be feeling hot all the time. They're going to be losing weight, diarrhea, sweating all the time. And they feel very anxious. And they feel like their heart's beating very fast and having flutters and things like that. So two different pictures, and that's where you start with diagnosing these patients.
So if you have a patient with high TSH and low T3/T4 also with the symptoms of hypothyroidism, this is consistent with primary hypothyroidism. Now, if you have a patient with elevated TSH and elevated free T3 and free T4 plus the symptoms of hyperthyroidism-- and usually a headache, because it's usually coming from a tumor in the head-- this is more consistent with a TSH-secreting tumor or secondary hyperthyroidism. And we should get an MRI of the brain to see where this tumor is. |
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Term
Diagnosis
• Elevated TSH and low free T3 and T4 |
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Definition
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Term
Diagnosis
• Elevated TSH and elevated free T3 and T4 |
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Definition
Symptoms of hyperthyroidism +/- headache
• MRI of the brain to localize tumor
• TSH secreting tumor |
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Term
Treatment
• Secondary Hyperthyroidism |
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Definition
• Treat with somatostatin analog prior to surgery to make euthyroid and possibly shrink tumor
• Octreotide, lanreotide |
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Term
Treatment
• Primary Hypothyroidism |
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Definition
| Thyroid hormone replacement |
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Term
Low TSH state
• Primary hyperthyroidism |
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Definition
| Elevated free T3/T4, suppressed TSH |
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Term
Low TSH state
• Secondary hypothyroidism |
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Definition
| Suppressed TSH and free T3/T4 |
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Term
Low TSH state
• Tertiary hypothyroidism (rare) |
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Definition
| Suppressed TSH and free T3/T4 |
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Term
| TRH (protorelin) stimulation test |
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Definition
*no longer used in the United States
• Administer IV TRH
• Measure TSH at time intervals
• If increase in TSH -> hypothalamic or tertiary
• If no increase in TSH -> pituitary or secondary
Low TSH state |
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Term
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Definition
Levothyroxine replacement (up to 1.6 mcg/kg/day)
• DO NOT MONITOR TSH in CENTRAL HYPOTHYROIDISM
• Monitor FT4 levels |
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Term
Gonadotropins (LH/FSH)
• GnRH -> + LH/FSH |
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Definition
• LH/FSH ->+ ovulation + estrogen production
• LH/FSH -> + testicular growth + testosterone production |
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Term
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Definition
HPG axis
So here is a picture of the HPG axis, so hypothalamic-pituitary-gonadal axis. And just like the other [? axes, ?] you have the hypothalamic hormone feeding to the pituitary, which then goes to the target organs. And then the estrogen, and progesterone, and testosterone have negative feedback to the pituitary and the hypothalamus. |
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Term
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Definition
- Primary hypogonadism
• Low estrogen/tesotsterone and high LH/FSH
- Secondary causes (LH/FSH secreting pituitary tumors) - very rare
• High LH/FSH, high testosterone, estrogen |
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Term
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Definition
• Exogenous use of testosterone or estrogen (suppression)
• Primary tumor secreting sex hormones (suppression)
• Secondary Hypogonadism (low LH/FSH, low sex hormones)
- Non-functioning pituitary tumor
• Hyperprolactinemia -> inhibits LH/FSH
• Tertiary Hypogonadism (low LH/FSH, low sex hormones) |
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Term
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Definition
• Primary vs. “Central”
• Do not do dynamic testing for the most part
• Can do imaging of the pituitary to see if any tumors and check the rest of the pituitary hormones as well
• Stress, opiates, anorexia, chronic systemic illness, and critical illness all cause “central” picture of hypogonadism- Don’t check levels in the hospital |
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Term
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Definition
- Primary hypogonadism
• Replace estrogen or testosterone
- Central Hypogonadism
• Shrink/Remove tumor
• Dopamine agonists for hyperprolactinemia • GnRH agonist
• Clomiphene (stimulates GnRH -> LH/FSH)
• Estrogen (OCP) or testosterone if no fertility desired |
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Term
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Definition
• GHRH -> + GH -> + IGF-1 (liver) ->
• growth, protein synthesis, cellular replication |
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Term
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Definition
| Here is the growth hormone feedback loop. And some of the growth hormone disorders are gigantism. So gigantism is an excessive amount of growth hormone. Usually, it's caused by a tumor that's secreting growth hormone. And we call it this when you have the increased growth hormone levels before puberty and before the growth plates fuse. |
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Term
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Definition
increased growth hormone before puberty
• Prior to growth plates fusing
• Large body stature, increased height + acromegaly symptoms |
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Term
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Definition
increased growth hormone after puberty
• Large hands, enlarged forehead and jaw, enlarged tongue, spreading teeth, arthritis, HTN, DM2, heart enlargement |
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Definition
| • Short height (children), hypoglycemia, osteoporosis, decreased muscle mass, decreased energy |
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Term
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Definition
| • Most cases of GH excess are caused by GH secreting tumors in the pituitary |
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Term
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Definition
- GH is not a reliable test given the episodic nature of it’s release (10% of patient’s with acromegaly have normal range values).
- Serum IGF-1 is the single best test for diagnosis. These values to not vary from hour to hour
- OGTT
• Measure GH before and 2 hours after 75 G
glucose administration
• Normal patients suppress GH <1 ng/mL
• Specific
• Gold standard for monitoring success after surgery |
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Term
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Definition
• Surgery **
• Radiation therapy
• Somatostatin analogues
- Octreotide, Lanreotide
- Can shrink size of adenoma too
• Growth Hormone receptor antagonists
- Pegvisomant |
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Term
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Definition
• Treat children before the epiphyses close - > the sooner the treatment, the better the response.
• Can treat adults if they benefit symptomatically
- Different guidelines have different recommendations |
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Term
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Definition
| So prolactin is I believe our last anterior pituitary hormone that we'll go over. So here is what happens with prolactin. It is secreted by the anterior pituitary and then stimulates milk synthesis. I'm sorry. Yes, milk synthesis. And then dopamine inhibits prolactin. |
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Term
| Hyperprolactinemia - Symptoms |
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Definition
• Galactorrhea
• Headache
• Visual field abnormalities
• EOM weakness
• Other anterior pituitary abnormalities
• Menstural irregularity
• Infertility
• Impotence |
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Term
| Hyperprolactinemia - Causes |
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Definition
• Prolactinoma (prolactin-secreting adenoma) • Pregnancy
• Trauma
• CKD
• Stalk effect
- Compression of the stalk and disruption of dopamine inhibition
• Medication induced (most common)
- Dopamine antagonists
- H2 receptor blockers
- TCAs
- Opiates |
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Term
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Definition
• AM fasting prolactin level
• Usually we get am fasting testosterone or estrogen, LH/FSH levels as well
• Prolactin levels > 100 indicate adenoma
• MRI brain (dedicated pituitary imaging)
• Medical treatment is FIRST LINE
• Dopamine agonists:
- Cabergoline
- Bromocriptine
• Surgical treatment only if medical treatment fails or patient cannot tolerate medical treatment |
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Term
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Definition
| So quickly on the posterior pituitary, ADH and oxytocin, like I said, are made in the hypothalamus, stored in the posterior pituitary. And they have their various functions. ADH has water and sodium balance in the kidney. And oxytocin is mostly functioning in milk letdown in lactating mothers. |
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Term
| Posterior Pituitary ADH Disorders |
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Definition
Diabetes Insipidus
-central
-nephrogenic
Syndrome of Inappropriate Antidiuretic Hormone (SIADH) |
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Term
Central Diabetes Insipidus
• Causes |
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Definition
• Idiopathic (up to 50%)
• Damage to the neurohypophysis from trauma, surgery, or radiation
• Familial
• Hemorrhage
• Infiltrative disorders (rare)
- Granulomatous disease
- Metastasis
- Infectious
- Lymphocytic Hypophysitis (autoimmune) |
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Term
Central Diabetes Insipidus
• Symptoms |
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Definition
• Polyuria
• Polydipsia
• Nocturia
• No evidence of renal disease
• Shock/ecephalopathy if no access to water |
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Term
Central Diabetes Insipidus
• Laboratory Values: |
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Definition
• ADH low or undetectable
• Serum sodium and osmolality are high
• Urine sodium and osmolality are low |
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Term
| Central Diabetes Insipidus vs Nephrogenic |
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Definition
• Central DI will be responsive to vasopressin
• If not responsive -> consider nephrogenic DI.
• Treatment is to administer vasopressin, drink to thirst, monitor electrolytes, I/Os, urine/serum osmolality. |
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