Endocrine Part 1 Adrenal, Thyroid Flashcards
(99 cards)
1
Q
A Closer Look at Hormone Function
- Releasing hormones from _____ – can be ____tory or ____tory -> anterior pituitary or posterior pituitary
- Posterior pituitary releases only (1) (considered more part of the nervous system bc made up of axons)
A
- Releasing hormones from hypothalamus – can be inhibitory or excitatory -> anterior pituitary or posterior pituitary
- Posterior pituitary releases only argenine vasopressin (considered more part of the nervous system bc made up of axons)
2
Q
How Hormones Transmit their Signals
-
Water soluble: our ____ or ____ derived hormones travel on their own (insulin, parathyroid hormone) – bind _____ cell surface receptors and acts through the (1) system
- (1) hormone is the only exception, is lipid soluble, and needs a binding globulin + nuclear receptor
- Lipid soluble: our ______ derived hormones (corticosteroids, sex hormones testosterone, estradiol) have to – binds to (1) receptors and act through (1)
A
-
Water soluble: our amino acid or protein derived hormones travel on their own (insulin, parathyroid hormone) – bind directly cell surface receptors and acts through the second messenger system
- Thyroid hormone is the only exception, is lipid soluble, and needs a binding globulin + nuclear receptor
- Lipid soluble: our cholesterol derived hormones (corticosteroids, sex hormones testosterone, estradiol) have to – binds to nuclear receptors and act through gene transcription
3
Q
Hypothalamic/Anterior Pituitary/End Organ Chart
A
4
Q
The Adrenal Cortex – Anatomy and Imaging
Imaging of choice to visualize adrenals (2)
Look for th_____, n______
- Signs of non-concerning/functional adrenal nodule =
- Signs of a concerning nodule =
A
CT or MRI (cannot visualize with US)
Thickening, Nodules
- Homogenous, lipid rich
- Heterogenous, non lipid rich interior, bright and dark signal – worrying about pheochromocytoma, adrenal cortical carcinoma, mets from other areas, anything >4cm is concerning, not being smooth
5
Q
Adrenal Cortex Homeostasis
Hypothalamic hormone (1) → Pituitary hormone (1) → acts on
If the hypothalamus is damaged, can aldosterone still be released?
- Glomerulosa to secrete (1) → acts on (1) receptor
- Fasciculata to secrete (1) → acts on (1) receptor
- Reticulosa to secrete (1) → acts on (1) receptor
A
CRH → ACTH
YES, core regulation of aldosterone by the RAAS system
- Aldosterone → Mineralocorticoid receptor (MR)
- Cortisol (→ corticosteroid binding globulin) → Glucocorticoid Receptor
- Androgens (testosterone, sex hormone binding globulin) → Androgen Receptor
6
Q
Role of Aldosterone
The Adrenal Cortex- Role in Homeostasis
- Sodium _____ (preserves ____)
- Potassium ______
- R____-A____ mediated
A
- Sodium absorption (preserve volume)
- Potassium secretion
- Renin-ATII mediated
7
Q
Role of Cortisol
The Adrenal Cortex - Role in Homeostasis
- Fuel m_____ – Preserve glucose availability (f___) and increase supply (st___)
- Increase peripheral ______ resistance
- Increase Hepatic ______ Production (HGP)
- P_____ catabolism – substrates available for HGP
- ____lysis for HGP
- Physiologic effect on b____
- Anti-in_____, st____ responses
- W____ balance – needed to increase free water clearance
- CNS – m___, app____, sl____ stabilization
- Vascular responsiveness to vaso______
A
- Fuel metabolism – Preserve glucose availability (fasting) and increase supply (stress)
- Increase peripheral insulin resistance
- Increase Hepatic Glucose Production (HGP)
- Protein catabolism – substrates available for HGP
- Lipolysis for HGP
- Physiologic effect on bone
- Anti-inflammatory, stress responses
- Water balance – needed to increase free water clearance
- CNS – mood, appetite, sleep stabilization
- Vascular responsiveness to vasoconstrictors
8
Q
The Adrenal Cortex- Pituitary Control
(4) major things that trigger release of cortisol?
These serve the basis of how we expect the adrenals to respond to ____ - which is the THE critical question when evaluating an inpatient for adrenal insufficiency
A
Stress
Hypotension
Infection
Hypoglycemia
These serve the basis of how we expect the adrenals to respond to Illness - which is the THE critical question when evaluating an inpatient for adrenal insufficiency
9
Q
Cortisol Circadian Rhythm*
*This is the basis for the best test for an ambulatory patient when there is a concern about adrenal insufficiency – (1)
A
Basal 8am serum cortisol
(ACTH peaks 6-8am leading to burst of cortisol in the morning)
10
Q
Primary Adrenal Insufficiency
=
-
Invariably involves loss of adrenal (2) production as well
- This pathophysiology is how we will differentiate PAI from SAI
- The adrenal medulla is usually left _____
- Must be __lateral and involve destruction of __% of the gland before one develops signs or symptoms
A
Bilateral destruction of glucocorticoid producing capabilities of the adrenal cortex
-
Invariably involves loss of adrenal mineralocorticoid and androgen production as well
- This pathophysiology is how we will differentiate PAI from SAI
- The adrenal medulla is usually left intact
- Must be bilateral and involve destruction of 90% of the gland before one develops signs or symptoms
11
Q
Primary Adrenal Insufficiency Etiology
Most common cause (1)
(5) others
A
Auto-immune Adrenalitis (>70% USA)
- Infectious Adrenalitis (TB, HIV, Fungal, Bacterial - meningococcus/waterhouse friedrichson sx)
- Carcinoma of lung, renal, breast (rare)
- Hemorrhage or Thrombosis (very rare) (sepsis (meningococcus, pseudomonas, staph, s pneumo), Warfarin mediated, Antiphospholipid syndrome)
- Drugs (rare) (ketoconazole, ICI, mitotane,) CAH (congenital adrenal hyperplasia)
12
Q
Primary Adrenal Insufficiency Manifestations*
Destruction of which layers of the cortex?
(2) Differentiating symptoms*
A
Destruction of all three layers of adrenal cortex
Hyperpigmentation dt excess ACTH
Hyperkalemia dt mineralcorticoid deficiency
13
Q
Secondary Adrenal Insufficiency
=
- No effect on (1) → no (1)
- May be (1) or (1) in origin
- Reduced production of ACTH - no (1)
- Overtime, the lack of adrenal stimulus by ACTH causes _____ of the adrenal glands
A
Interruption of the hypothalamic-anterior pituitary axis such that a deficit in cortisol production occurs
- No effect on aldosterone – no hyperkalemia
- May be hypothalamic or pituitary in origin
- Reduced production of ACTH – no hyperpigmentation
- Over time, the lack of adrenal stimulus by ACTH causes atrophy of the adrenal glands
14
Q
Secondary Adrenal Insufficiency Etiology
(2)
A
Exogenous Glucorticoid Administration (main cause)
Any cause of Hypopituitarism (2nd most common cause- pituitary adenomas)
15
Q
Exogenous Glucocorticoids in Secondary AI
- Potential Routes =
- Many im_____ algorithms – duration (>__ weeks) and dose (>__ mg prednisone) play a significant role – but nothing has been clinically defined
- There is no clear recommendation for “_____” down a dose to prevent SAI – but ch____ of use, d____, fr____, interfering m_____ and in____ for therapy all play a role
A
- Oral, ocular, inhaled, transdermal, rectal, or parenteral routes
- Many imperfect algorithms – duration (>3 weeks) and dose (>5 mg prednisone) play a significant role – but nothing has been clinically defined
- There is no clear recommendation for “titrating” down a dose to prevent SAI – but chronicity of use, dose, frailty, interfering medications and indication for therapy all play a role
16
Q
Causes of Hypopituitarism in Secondary AI
- T____, craniopharyngioma, ra_____, pituitary su____
- In_____ diseases – Sarcoidosis, Hereditary Hemochromatosis, Histiocytosis X
- Lymphocytic hy____ – Auto-immune, pregnant women
- Post-partum pituitary n_____
- Head tr____
- Dr___ - ICI
A
- Tumors, craniopharyngioma, radiation, pituitary surgery
- Infiltrative diseases – Sarcoidosis, Hereditary Hemochromatosis, Histiocytosis X
- Lymphocytic hypophysitis (inflammation of pituitary gland) – Auto-immune, pregnant women
- Post-partum pituitary necrosis
- Head trauma
- Drugs - ICI (intracavernosal injection)
17
Q
Adrenal Insufficiency Non-Specific Symptoms
(seen in both types of AI)
- F_____, listlessness, f___, abdominal p___, n____, ____ appetite, em____, generalized w____ness, d____ness
- Weight ____
- _______ hypotension
-
Concerning symptoms –(3)
- If a patient with a known history of AI calls with these symptoms – it is clinically reasonable to assume they are in adrenal _____
A
- Fatigue, listlessness, fever, abdominal pain, nausea, poor appetite, emesis, generalized weakness, dizziness
- Weight loss
- Orthostatic hypotension
-
Concerning symptoms – fever, N/V, abdominal pain
- if a patient with a known history of AI calls with these symptoms – it is clinically reasonable to assume they are in adrenal crisis
18
Q
Manifestations Specific to Primary AI
(2)
1st symptom, specifically where?
A
Skin Hyperpigmentation
(Palms, dorsal surface of hands, buccal mucosa, sun-exposed areas)
Salt Craving
19
Q
Associated Symptoms of Secondary AI
Any symptom of hypopituitarism
- Hypo_____ - sexual dysfunction, loss of libido, ED, oligo- or amenorrhea
- Hypo_____ – cold intolerance, constipation, fatigue
- (1) hormone deficiency – not clinically apparent in adults
- (1) – polyuria, thirst
- _____ effect – Headache, Visual Field deficits
A
- Hypogonadism - sexual dysfunction, loss of libido, ED, oligo- or amenorrhea
- Hypothyroidism – cold intolerance, constipation, fatigue
- GH deficiency – not clinically apparent in adults
- DI – polyuria, thirst
- Mass effect – Headache, Visual Field deficits
20
Q
Adrenal Insufficiency - Lab Evaluation
Why are these levels low or elevated?
- Na =
- K+ =
- Glucose =
- BP =
- WBC =
A
- Hyponatremia dt cortisol/aldosterone deficiency (salt wasting - only in primary)
- Hyperkalemia and Metabolic Acidosis (only in primary)
- Hypoglycemia
- Hypotension dt salt wasting w concomitant volume depletion/inability to maintain vascular tone from cortisol deficiency
- Eosinophilia
21
Q
Adrenal Insufficiency Diagnostics
There may not be a true gold standard, recall the circadian rhythm
(2)*
- For inpatient ?
- After diagnosis made, try to establish level of defect by using ACTH
- Primary - _____ ACTH
- Secondary - _____ ACTH
A
Basal 8am serum cortisol
ACTH stimulation tests
- For inpatient use cortisol levels independent of time
- After diagnosis made, try to establish level of defect by using ACTH
- Primary - elevated ACTH
- Secondary - low or normal ACTH
22
Q
ACTH Stimulation Testing
=
A
Your pretty much giving a bolus of ACTH and see if adrenals can make cortisol
If primary → still won’t make it bc destruction is in the adrenals
If secondary → can probably make cortisol bc using synthetic ACTH
23
Q
Basal 8am Cortisol and ACTH Diagnostic Levels
Cortisol level diagnostic for AI?
Cortisol level that rules out AI?
ACTH levels diagnostic for primary AI?
ACTH levels diagnostic for secondary AI?
A
Cortisol <3mcg/dL ~100% specific for AI
Cortisol >16mcg/dL ~100% rules out AI
ACTH >100pg/mL seen uniformly in primary AI
ACTH low/normal in secondary AI
24
Q
Indeterminate Basal Cortical Levels
Between __ - __
- For patients whose time is of the essence?
- Most useful form of emergent/urgent ACTH stimulation test =
A
Cortisol levels between 3-16mcg/dL
- Test can be performed at any time of day since there is no diurnal variation in response to ACTH
- High dose, short ACTH stimulation test = 250mcg cosyntropin and drawing plasma cortisol at time 0 and 60min
25
Interpreting High Dose ACTH Stimulation Test
Normal result =
Abnormal result =
Peak cortisol \>16mcg/dL
Failure to reach a cortisol of \>16mcg/dL is diagnostic of AI
(but have to wait for ACTH level to return to know if PAI or SAI)
26
Primary AI Treatment
**(2)** **Glucocorticoid replacement**, frequency of dosing?
XX (1) XX
**(1)** **Mineralcorticoid replacement for management of (2)**
1. **Hydrocortisone** 10-20mg AM/5-10mg PM (shorter half life)
2. **Prednisone** 2.5-7.5 at bedtime (longer half life)
NO dexamethasone bc so potent can Cushing's
1. **Fludrocortisone** 0.05-0.2mg daily for management of **BP and K+**
27
Secondary AI Treatment
\_\_\_\_\_\_\_ replacement only, which is first choice?
(2)
Glucocorticoid replacement only, **hydrocortisone is first choice**
**Hydrocortisone** 10-15mg AM/5-10mg early PM
**Prednisone** 2.5-7.5 at bedtime
28
AI Home Precautions
1. **Medic-Alert \_\_\_\_\_/Fit-bit t\_\_\_**
2. **\_\_\_\_ or ____ dose rules for stress**
3. Rx (1) (or other glucocorticoid) emergency 100 mg IM injection ___ at home **(1)**
4. If unable to take PO\* pills- use the (1) and call for emergency assistance
\*sign of impending adrenal crisis
1. **Medic-Alert bracelet/Fit-bit tag**
2. **Double or Triple dose rules for stress**
3. Solumedrol (or other glucocorticoid) emergency 100 mg IM injection kit at home Act-o-Vial
4. If unable to take PO\* pills- use the Act-o-Vial and call for emergency assistance
* Home stress like flu, gastroenteritis – will need to double or triple glucocorticoid dose – to mimic increased stress response*
* Act-O-vial – fam member is the one that gives it, then call 911*
29
Adrenal Crisis Symptoms and Labs
Symptoms
* **\_\_\_\_\_\_\_\_ followed by ____ (usually refractory to fluids and pressors)**
* **Abdominal p\_\_\_\_and em\_\_\_**
* **O\_\_\_\_\_\_ hypotension and severe \_\_\_\_ness**
* **F\_\_\_\_**
* **Con\_\_\_\_**
**Clinical lab findings**
* **\_\_\_\_\_natremia**
* **\_\_\_\_\_glycemia**
Symptoms
* **Hypotension followed by shock (usually refractory to fluids and pressors)**
* **Abdominal pain and emesis**
* **Orthostatic hypotension and severe weakness**
* **Fever**
* **Confusion**
**Clinical lab findings**
* **Hyponatremia**
* **Hypoglycemia**
30
Adrenal Crisis Treatment
(3)
**Aggressive IVF (2-3 liters bolus)**
**Hydrocortisone 100 mg iv t.i.d.**
**Treat underlying illnesses with Antibiotics, ICU admission**
31
Diseases of Adrenal Cortical Excess
(3)
**Hyperaldosteronism (Conn's Syndrome)**
**Hypercortisolism (Cushing Syndrome)**
**Hyperandrogenism**
32
Hyperaldosteronism (Conn's Syndrome)
Etiology (1) vs. (1)
* BP =
* Na _____ and K \_\_\_\_\_
Adenoma vs bilateral hyperplasia
* Hypertension
* Na retention and K secretion (hypokalemia)
33
Hypercortisolism (Cushing's Syndrome)
ACTH dependent most common cause (1)
ACTH independent causes (2)
Pseduo-Cushing's Syndromes (3)
* My\_\_\_\_\_of symptoms
Pituitary tumor that releases extra ACTH
Adrenal adenoma or carcinoma , Exogenous administration
Alcoholism, Depression, Obesity
* Myriad of symptoms
34
Hyperandrogenism
Etiology **(1)** seen more commonly than (1)
* Excess of DHEAS/\_\_\_\_\_ causing viralization
**Adrenal cortical carcinoma** seen more commonly than adenoma
* Excess of DHEAS/Testosterone causing viralization
35
Cushing's Syndrome Manifestations
*More truncal \_\_\_\_\_, extremities \_\_\_\_*
1. Weight =
2. Hair =
3. Bone =
4. Face =
5. BP =
6. Abdominal skin =
7. Muscle =
8. Ankle =
9. Immune =
*Truncal obesity, thin extremities*
1. Weight gain
2. Hirsutism
3. Fractures
4. Moon Facies
5. Hypertension
6. Abdominal red-purple striae
7. Muscle weakness
8. Ankle edema
9. Immune suppression (fungal infections)
36
Cushing's Syndrome Definition
=
A group of diseases whose common theme is excess glucocorticoid exposure
Patho includes an exacerbation of the underlying actions of glucocorticoids
37
Cushing's Syndrome Loss of Circadian Rhythm
What happens to normal cortisol levels around midnight?
In Cushing's how do we test for a loss of this nadir?
Nadir of cortisol at midnight
**Midnight salivary free cortisol using cotton swab** since midnight plasma cortisol is not really feasible (normally should be low, but will be high in Cushing's)
38
Dexamethasone Suppression Test
=
Low-Dose DST =
Give 1mg dexamethasone at midnight, comes to lab the next morning to test 8am cortisol – should have low cortisol (\<2 mcg/dL) bc you're suppressing the normal HPA axis, but pts with Cushings will still have high cortisol
Also can be done using 0.5mg Q6 for 48 hours
39
How do we quantify an abnormal level of free cortisol?
3rd test for Cushing's
**24 hour urine free cortisol**
(is the quantitative integrated measure of cortisol production in a single day)
(since circadian rhythm makes a morning cortisol insufficient evidence of an excess in cortisol and \>90% is bound to CBG/Alb-any excess beyond capacity of CBG/Alb will be free and excreted in urine)
40
Cushing's Screenings Summary
Variable sensitivity and specificity of each test depending on value used for diagnosis- ask yourself these questions
Should cortisol be high in the saliva at midnight?
Should cortisol be detectable if we are giving the patient exogenous steroids?
Should cortisol be detectable in excess in the urine?
Late night salivary cortisol should be undetectable
1mg dexamethasone should show low AM cortisol
24 hour urine free cortisol should be within the normal range
41
Assess for ACTH dependency in Cushing's
Once someone tests + for a Cushing's Syndrome screening test
* ACTH levels suppressed =
* ACTH levels detected =
* CT Adrenals (consider macronodular hyperplasia)
* MRI of pituitary → transphenoidal hypophysectomy
42
Endocrine Hypertension - RAAS
Aldosterone acts on the ____ tubule to?
Aldosterone acts on the distal tubule to resorb sodium and excrete potassium
43
Primary Aldosteronism
=
Effects:
1. BP =
2. Sodium =
3. Potassium =
4. H+ excretion → metabolic \_\_\_\_\_
5. Pleiotropic effects – inflammation, microangiopathy, fibrosis
6. ______ of plasma renin activity
7. Aldosterone escape (a ____ in response to the expanded ECF) will prevent edema from developing, but ___ persists
8. Increased risk of _____ disease (MI, CVA, A Fib) and chronic kidney disease
**“Inappropriately high aldosterone production, relatively _autonomous_, _non-suppressible_ by sodium loading”**
1. Hypertension
2. Sodium retention
3. Potassium excretion → hypokalemia
4. H+ excretion → metabolic alkalosis
5. Pleiotropic effects – inflammation, microangiopathy, fibrosis
6. Suppression of plasma renin activity
7. Aldosterone escape (a diuresis in response to the expanded ECF) will prevent edema from developing, but HTN persists
8. Increased risk of cardiovascular disease (MI, CVA, A Fib) and chronic kidney disease
44
Who to test for Primary Aldosteronism (Endocrine Hypertension)
Prevalence of 5-10% of all HTN pts
1. **Age =**
2. **Masses on \_\_\_\_\_**
3. **\_\_\_\_\_ HTN** (\>3 drugs poorly controlled, 4 drugs needed to control)
4. **\_\_\_\_\_ HTN** (\>150/100)
5. **Potassium =**
6. ____ **History**
1. **Young** (early onset HTN or stroke)
2. **Adrenal masses**
3. **Resistant HTN**
4. **Severe HTN**
5. **Hypokalemia**
6. **Fam hx**
45
Primary Aldosteronism Tests
Morning, seated, normokalemic levels of plasma (2), (1) ratio
Plasma Aldosterone Concentration
Plasma Renin Activity
PAC/PRA: Aldosterone Renin Ratio (ARR)
46
Interpretation of Aldosterone/Renin Tests
**Primary Aldosteronism will show =**
Secondary Aldosteronism will show =
Other Mineralcorticoid excess will show =
**High Aldo, Low Renin**
High Aldo, High Renin
Low Aldo, Low Renin
47
Treatment for Primary Aldosteronism
Aldosterone Producing Adenoma (APA) tx =
Idiopathic Bilateral Adrenal Hyperplasia tx =
Surgery cures the disease, HTN improves in 30-60% of patients
Medically treated as surgery does not cure the disease (and causes primary adrenal insufficiency)
48
Aldosterone Producing Adenoma Treatment
**(1)**
100 % cure of \_\_\_\_\_
30 – 60% cure of \_\_\_\_
Residual HTN after surgery is usually _____ HTN
**Unilateral adrenalectomy**
## Footnote
100 % cure of hypokalemia
30 – 60% cure of HTN
Residual HTN after surgery is usually essential HTN
49
Bilateral Adrenal Hyperplasia Pharm Therapy
(1)-(2)
Aldosterone receptor antagonists
## Footnote
**Spironolactone**
**Epleronone**
50
How to perform a Thyroid Exam?
(3) lobes of thyroid + the (1)
Thyroid gland engulfs the (1)
Stand behind patient and place 3 middle fingers of both hands along midline of neck below chin and gently walk them down.
Right, Left, Pyramidal Lobe, Isthmus
Cricoid cartilage
51
Thyroid Hormone Metabolism
Hypothalamus secretes (1) →
Pituitary secretes (1) →
Thyroid secretes (2) →
Which is the dominant hormone?
Travels through circulation using (1) made by the Liver, ____ hormone is what inhibits pituitary from releasing more TSH
Hypothalamus secretes TRH
Pituitary secretes TSH
Thyroid secretes T3, T4
T4 is the dominant hormone
Travels through circulation using binding globulins made by liver, free hormone is what inhibits pituitary from releasing more TSH
52
Producing Thyroid Hormone
Thyroid hormone is stored in the _____ →
Through (1) transcription, uses (1) which adds iodine to protein and produces T3 and T4 using (1)
Thyroid hormone is stored in the colloid →
Through mRNA transcription, uses thyroid peroxidase (TPO) which adds iodine to protein and produces T3 and T4 using thyroglobulin (Tg)
53
Transport of Thyroid Hormone
Bound hormone =
Unbound hormone =
Which is the most important level?
* ____ in TBH = **Estrogen**, acute hepatitis, drugs, inherited D/O
* ____ in TBG = **Androgen, Nephrotic syndrome, Cirrhosis,** glucocorticoids, inherted D/O (XLR)
Bound hormone = Inactive form (99%)
Unbound hormone = Free Active form
**Free T4 is the most important level**
* Increase in TBG = **Estrogen**, acute hepatitis, drugs, inherited D/O
* Decrease in TBG = **Androgen, Nephrotic syndrome, Cirrhosis,** glucocorticoids, inherted D/O (XLR)
54
T4 and T3 Production
T3 is produced in the _____ and is converted into T3 from \_\_\_
**Takeaway: Always measure (2)\*\***
T3 is produced in the periphery and is converted into T3 from T4
## Footnote
**Always measure Free T4 and TSH\*\***
55
Role of Thyroid Hormone
1. Fetal ____ Development/C\_\_ and S\_\_\_\_\_Maturation
2. Basal metabolism =
3. Cardiac effects =
4. Sympathetic Nervous System =
5. Pulmonary =
6. Hematopoietic =
7. Gastrointestinal =
8. Skeletal =
9. Neuromuscular=
10. Fuel metabolism – passive hormone – needed but not the primary role of T4/T3 =
11. Endocrine =
1. Fetal Brain Development/CNS and Skeletal Maturation
2. O2 consumption and Heat Production
3. Positive inotropic and chronotropic effects, Enhanced Adrenergic sensitivity
4. Increase in B-adrenergic receptors and enhances sensitivity to catecholamines
5. Permissive responses to hypoxia and hypercapnia
6. Erythropoiesis
7. Gut motility
8. Bone turnover (promotes resorption \> formation)
9. Muscle contraction and relaxation
10. Hepatic gluconeogenesis and glycogenolysis, Lipid synthesis and turnover
11. Production, responsiveness and metabolic clearance of hormones
* Thyroid hormone does pretty much everything*
* Lack of thyroid hormone -\> gut motility goes down – risk for ileus, risk for fractures*
56
Tests of Thyroid Function
(2) most important
* (1) binding protein dependent, used mostly for pregnancy
* (1) not a useful assessment in most cases, peripheral production
**TSH -** the most informative test, very sensitive, always to be done with measurement of peripheral hormone…
**Free T4 -** unbound biologically important portion
* Total T4-binding protein dependent, used mostly for pregnancy
* Free T3-not a useful assessment in most cases, peripheral production
57
Tests of Thyroid Autoimmunity
**(1)\*** commonly seen in Hashimotos, but a general marker for thyroid autoimmunity
* (1) as above, but less commonly positive
* (1) specific marker of Grave's disease
* (1) aka thyrotropin binding inhibitory immunoglobulin (TBBII) - also specific for Graves disease
**TPO (thyroid peroxidase antibody)**
* Thyroglobulin Ab
* TSIg (thyroid stimulating immunoglobulin) - Graves
* TRAbs (TSH Receptor antibodies) - Graves
58
Thyroid Imaging
**(1)\***
Functional Testing
**(1)\***
**US** (assesses for echogenicity, nodularity, vascularity)
Uptake and Scan - usually for hyperthyroidism
59
Hypothyroidism
=
Most common primary etiologies (4)
T4, TSH levels =
A clinical condition of reduced or absent thyroid hormone production
**Hashimoto's** (autoimmune) most common
**Total thyroidectomy** (iatrogenic)
**RAI I131 therapy** (iatrogenic)
**Iodine Deficiency**
**Low T4, High TSH**
60
Primary vs. Secondary Hypothyroidism
Primary Hypothyroidism =
T4 and TSH levels =
Secondary Hypothyroidism =
T4 and TSH levels =
Destruction of thyroid gland, Low T4, High TSH
Underactive pituitary gland, Low T4, Low TSH
61
Hashimoto's Hypothyroidism
=
1. Most common cause of (1)
2. **General population antibody __ prevalence can range from 8-27%**
3. Risk of hypothyroidism increases with (1) +Ab, but is still low 2-4%/year
4. More common in what gender?
5. **Associated with other _____ diseases** (T1\_\_\_, Add\_\_\_\_\_, Vit\_\_\_\_\_, Pernicious ______ and ____ areata)
6. Can see other thyroid antibodies such as (1)
7. What is seen on histology?
B and T cells launch autoimmune attack and damage normal thyroid cells, damaged thyroid leaks hormones
1. Most common cause of primary hypothyroidism
2. **General population antibody + prevalence can range from 8-27%** *(but do not have Hashimoto's)*
3. Risk of hypothyroidism increases with TPO +Ab, but is still low 2-4%/year
4. **More common in women**
5. **Associated with other autoimmune diseases** (T1DM, Addison's, Vitiligo, Pernicious anemia, Alopecia areata)
6. TSH receptor antibodies can also be seen
7. Lymphocytic CD4, CD8 T cells, and B cells **infiltration** *(purple patches in pic)*
62
Hypothyroidism Symptoms
1. General =
2. Weight =
3. Extremities =
4. Temperature intolerance =
5. Muscle =
6. GI =
7. Voice =
8. Menses =
9. Sweating =
1. Fatigue and listlessness, slowed mentation
2. Weight gain – usually with a poor appetite
3. Edema
4. Cold intolerance
5. Proximal muscle weakness
6. Constipation
7. Hoarseness – accumulated fluid in the vocal cords
8. Menorrhagia, Irregular menses or amenorrhea
9. Decreased sweating
63
Hypothyroidism Signs
1. Affect =
2. Skin =
3. Hair and Nails =
4. Eyes/Extremities =
5. BP, HR =
6. Myocardial contractility =
1. Depressed affect
2. Cold dry skin
3. Brittle hair and nails
4. Periorbital/LE edema (non-pitting)
5. HTN, Bradycardia
6. Decreased myocardial contractility
64
Lab Findings in Hypothyroidism
1. Hgb =
2. Na =
3. LFTs =
4. Inflammatory markers =
5. Lipid panel =
1. Anemia
2. Hyponatremia
3. Abnormalities in liver enzymes
4. Increased CK
5. Hypercholesterolemia and Hypertriglyceridemia
65
Consequences of Untreated Hypothyroidism
**End stage hypothyroidism =**
* \_\_\_\_cholesterolemia, An\_\_\_\_
* Cardiac, Pulmonary =
* Neuro =
**Myxedema Coma**
* Hypercholesterolemia, Anemia
* CHF, effusions
* Neurologic abnormalities
66
Hypothyroidism Treatment
**(2) Rx**
Which is not recommended, and why?
Target range?
**Levothyroxine** (Synthroid) - LT4
**Liothyronine** LT3 \<3/LT4 combo
Liothyronine not recommended bc risk of overtreatment
\*At target range is defined by medical conditions, age and other factors *(elderly naturally have higher TSH lvls so normal is around 4, theres is 7-8)*
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Levothyroxine Dosing
## Footnote
**\_\_\_\_mcg/kg = full replacement**
**Slow replacement recommended for populations at risk for CVD/arrhythmia, particularly (2)**
**What happens if you miss a dose?**
**1.6mcg/kg = full replacement**
**Slow replacement for \>60, CVD/TD2M patients**
T4 has a long half life of 7 days, so **missed doses can be given on subsequent days**
*Takes 5 weeks to get to steady state*
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Hypothyroidism Tx Follow Up
\_\_ week re-check of TFTs after any dose change
Goal for Primary hypothyroidism – At ____ range\* (2) values
Goal – Secondary hypothyroidism – \_\_\_-level of normal ___ range
6 week re-check of TFTs after any dose change
Goal for Primary hypothyroidism – At target range\* TSH and FT4
Goal – Secondary hypothyroidism – mid-level of normal FT4 range
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Levothyroxine Patient Education
When to take it, how?
Do not take with?
If you miss a dose?
Any change in pill (1) or (1) begets a call
Do not take b\_\_\_\_ within 5 days of having labs drawn
On an empty stomach, 60 min before food or drink, with water only (can be given 2-3 hrs after last meal if more convenient)
Do not take with iron, calcium, soy, other otc, herbals, supplements, prenatal/multi vitamins (is a drug that easily interacts with other things, educate to take alone!)
Okay to take as soon as you remember or following day
Any change in pill color or shape begets a call
Do not take with biotin within 5 days of having labs drawn
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Algorithm for Pts with Interference in Achieving Euthyroidism
1. Assess ad\_\_\_\_
2. Change in w\_\_\_\_?
3. Change in man\_\_\_\_?
4. Has the patient started supp\_\_\_\_ or new m\_\_\_\_?
5. Has there been a change in thyroxine (1)
6. Has there been a new diagnosis of \_\_\_itis or C\_\_\_\_ disease *(interfering with absorption)*
1. Adherence → pill box or toothbrush recommendation, reminders about safety of taking missed doses
2. Change in weight?
3. Change in manufacturer? (pill shape)
4. Has the patient started supplements or new medications? (absorption, metabolism, thyroiditis, hypophysitis)
5. Change in thyroxine binding globulin (typically estrogen mediated)
6. Gastritis or Celiac disease?
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Features of Myxedema Coma
Which symptom is directly correlated with mortality in some studies?
Hypothermia\*
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Treatment of Myxedema Coma
(controversial-no studies support any general recs)
**\_\_\_ stay is mainstay of therapy (5)**
(1) 100-500mcg IV once, then 50-100mcg daily
(1) 10-25mcg IV Q8, then 10mcg IV Q8
**ICU stay is mainstay of therapy**
**Antibiotics, Steroids, Ventilator support, Warming, Volume resuscitation**
Levothyroxine
Liothyronine (the one exception where we give T3)
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Condition where someone has normal T4 levels, but abnormal TSH
Generally, we will start thyroid hormone replacement if TSH \> \_\_\_
Subclinical Hypothyroidism
treat if TSH \>10
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Thyrotoxicosis
A medical condition of excess thyroid hormone levels
(3)\* most cases caused by endogenous overproduction by thyroid gland
**(1)** by release of preformed thyroid hormone from damage to gland
**(1)** exogenous administration
1. **Grave's Hyperthyroidism** (autoimmune stimulation of thyroid
2. **Toxic Nodule** (adenoma-Plummer's disease) or
3. **Toxic Multinodular goiter**
**Thyroiditis**
**Excess Levothyroxine administration** (thyrotoxicosis factitia or iatrogenic)
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Rare causes of thyrotoxicosis
* (1) producing pituitary adenoma
* (1) mediated hyperthyroidism - think glycoprotein a and B chains
* Drugs (3)
* TSH producing pituitary adenoma
* HCG mediated hyperthyroidism - think glycoprotein a and B chains
* Amiodarone, Iodine administration, ICI (Immune Checkpoint Inhibitors)
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Grave's Disease
**(1) stimulates the (1) receptor**
* **\_\_-**\_\_% of thyrotoxicosis
* More common in what gender?
* Risk factors: G\_\_\_\_ and En\_\_\_\_\_, sm\_\_\_\_\_, MZ rate \< than expected, HLA-DR
* TPO +?
**Thyroid Stimulating Immunoglobulin (TSIg) stimulates TSH-Receptors**
* **60-80**% of thyrotoxicosis
* More common in females
* Risk factors: Genetic and Environment, smoking, MZ rate \< than expected, HLA-DR\<
* TPO + in many cases
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Thyrotoxicosis Symptoms
1. **Pal\_\_\_\_\_\_\_**
2. **N\_\_\_\_\_\_ness**
3. **Ag\_\_\_\_\_\_ or irr\_\_\_\_\_\_**
4. **\_\_\_\_\_ intolerance**
5. **Tr\_\_\_\_\_**
6. Easy Fatigue
7. Muscle weakness
8. **Weight _____ with good appetite**
9. Blurry or Double Vision
10. **\_\_\_\_\_\_\_\_ bowel movements**
11. Oligomenorrhea
1. **Palpitations**
2. **Nervousness**
3. **Agitation or irritability**
4. **Heat intolerance**
5. **Tremor**
6. Easy Fatigue
7. Muscle weakness
8. **Weight loss with good appetite**
9. Blurry or Double Vision
10. **Frequent bowel movements**
11. Oligomenorrhea
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Grave's Disease Pathognomonic Findings
**(1) dt cytokines**
**(1) heard over thyroid gland**
**(1) found on tibia**
**Ophthalmopathy dt cytokines**
**Bruit/Thrill heard over thyroid gland**
**Pretibial Myxedema (NOT that myxedema)**
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Thyroiditis
Pattern of thyroid levels in Thyroiditis?
Etiologies
* Subacute painful causes = Post ____ infection (de Quervain), G\_\_\_\_ cell or Gran\_\_\_\_\_\_
* Acute thyroiditis = b\_\_\_\_\_ cause, symptoms include ____ pain, fluctuance, f\_\_\_, marked elevated \_\_\_\_
* **Painless (silent) thyroiditis - most common =** happens post-\_\_\_\_\_ (TPO+)
* Drug induced = **(1)\*,** Am\_\_\_\_\_\_, IFN a, post-\_\_\_\_\_\_ contrast load, RAI-131, usually painless
Hyperthyroid phase then falls to hypothyroid phase than back to normal (ppl will recover if just one episode)
* _Subacute painful causes_ = Post **viral** infection (de Quervain), Giant cell or Granulomatous
* _Acute thyroiditis_ = **bacterial** cause, symptoms include severe pain, fluctuance, fever, marked elevated ESR
* **_Painless (silent) thyroiditis_ - most common =** happens post-partum (TPO+)
* _Drug induced_ = **ICI\*,** Amiodarone, IFN a, post-iodinated contrast load, RAI-131, usually painless
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Thyrotoxicosis Signs
**(2)\* cardiac signs**
1. Goiter
2. Warm, moist skin
3. Proximal myopathy
4. Eye lid retraction
5. Gynecomastia (rare)
6. Systolic Murmur – high output CHF
7. Wide pulse pressure
**Tachycardia (ST most commonly)**
**Atrial arrhythmias – esp. A Fib**
1. Goiter
2. Warm, moist skin
3. Proximal myopathy
4. Eye lid retraction
5. Gynecomastia (rare)
6. Systolic Murmur – high output CHF
7. Wide pulse pressure
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Consequences of Untreated Hyperthyroidism
(3)\*
Others (4)
**A-Fib\***
**Osteopenia, Osteoporosis\***
**Thyroid Storm**
Tachycardia, CHF (high output), Angina, Death
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Importance of Eye Exam in Thyrotoxicosis
What is common to all forms of thyrotoxicosis?
What is only found in Graves?
Lid Retraction (white sclera exposed)
Proptosis
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Thyrotoxicosis Diagnostic Labs
## Footnote
**(2)\* most specific**
**TSIg (Thyroid stimulating immunoglobulin)**
**TBII (Thyrotropin binding inhibitory immunoglobulin)**
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Thyrotoxicosis Imaging
(1)\*
Explain?
(as long as pt is not pregnant)
Uptake and Scan
(where you give radioactive iodine and see if there is increased iodine uptake in the gland meaning that gland is actively making excess thyroid hormone)
top left (normal), bottom left (1 nodule), top right (graves nc bilateral)
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Hyperthyroidism Pharm Treatment
**(2)\*** first line therapy
**(1)\*** symptom relief
**Methimazole** or PTU
High dose **Beta Blockers**
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Methimazole and PTU Considerations
First line therapy for what type of patients ideally?
**Precautions for high doses?**
**Why is PTU not really used? except in (2) conditions**
Young, low risk patients or depletion therapy in eldery, high risk patients prior to I-131 or surgery
## Footnote
**Agranulocytosis precautions - head to ED with pill bottle for CBC if experiencing Fever or Infectious symptoms**
**3rd most common cause of liver toxicity by medication, rarely indicated except for 1st trimester of pregnancy or thyroid storm**
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Definitive Treatment for Hyperthyroidism
(2)-(1),(2)
**RAI 131** (radioactive iodine to destroy enough thyroid tissue to become euthyroid)
**Surgery - Total thyroidectomy** for Graves or TMNG, **Hemithyroidectomy** for toxic adenoma
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Tidbits of Hyperthyroidism Treatment
**Thionamides**
* Thionamide (ie. methimazole) **only inhibits production of ___ hormone, does not interfere w pre-formed hormone release**
* Thionamide use in a patient with (1) will only lengthen hypothyroid phase and cause confusion in interpreting TFT's
* So only use (2) to treat thyroiditis
**Beta Blockers**
* **BB in high doses are the drug of choice to treat which symptomatic relief and suppression of (1)**
* **Utilize BB up front and titrate agg\_\_\_\_\_\_\_**
* **Establish the _____ of thyrotoxicosis before initiating**
**Thionamides**
* Thionamide (ie. methimazole) **only inhibits production of new hormone, does not interfere w pre-formed hormone release**
* Thionamide use in a patient with thyroiditis will only lengthen hypothyroid phase and cause confusion in interpreting TFT's
* So only use BB and pain meds to treat thyroiditis
**Beta Blockers**
* **BB in high doses are the drug of choice to treat which symptomatic relief and suppression of tachyarrhythmia**
* **Utilize BB up front and titrate aggressively**
* **Establish the etiology of thyrotoxicosis before initiating**
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Hyperthyroidism Chart
Uptake is low in thyroiditis bc is damaged cells just leaking out – nothing to hold on to the radioactive iodine
90
Thyroid Storm
* Precipitated by?
* **Increased risk in in\_\_\_\_\_\_ treated thyrotoxicosis**
* Avoid point scoring systems – it is a _____ diagnosis!
* PS – if the patient is calm, afebrile and can take PO without nausea or emesis, it is almost assuredly ____ storm
* **If the patient is agitated, febrile and cannot take PO – treat as _____ until proven otherwise**
* High mortality from _______ causes
* These patients require the ICU
* Precipitated by **acute illness or insult**
* **Increased risk in in inadequately treated thyrotoxicosis**
* Avoid point scoring systems – it is a clinical diagnosis!
* PS – if the patient is calm, afebrile and can take PO without nausea or emesis, it is almost assuredly not storm
* **If the patient is agitated, febrile and cannot take PO – treat as storm until proven otherwise**
* High mortality from cardiovascular causes
* These patients require the ICU
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Thyroid Storm Treatment Algorithm
* High doses of **(1)** 40 – 60 mg PO q4H (or i.v. beta-blocker)
* High doses of **(1)** (PO, NG, PR enema) or PTU (T4-\>T3 effect)
* 1 hour after Thionamide dose – can give **(1)** solution ( it blocks thyroid hormone release)
* High dose **(1)** +/-
* High doses of **Propranolol** 40 – 60 mg PO q4H (or i.v. beta-blocker)
* High doses of **Methimazole** (PO, NG, PR enema) or PTU (T4-\>T3 effect)
* 1 hour after Thionamide dose – can give **Iodine** solution ( it blocks thyroid hormone release)
* High dose **steroids** +/-
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Treatment of Subclinical Hyperthyroidism
Takeaway =
Subclinical hypothyroidism, can be more lenient and watch but subclinical hyperthyroidism esp in elderly we are worried for A-fib
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Transient Gestational Thyrotoxicosis
Why does it happen? Do we treat it?
Happens bc early in pregnancy HCG levels are elevated which stimulate TSH receptors resulting in high T4
We don't treat it, will go away once HCG falls after 1st trimester
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Nodular Thyroid Disease
Commonly associated with what levels of FT4 and TSH?
Usually asymptomatic but monitor for **(4)** symptoms
Preferred imaging for substernal nodules **(1)**
Asymptomatic nodules need further workup to rule out? How? and especially for who?
Non-toxic/Euthyroid - normal FT4 and TSH
**Dysphagia, Dyspnea with arms raised or lying down, Hoarseness, Stridor**
CT neck and chest with contrast
Cancer, \>1cm usually need a FNA, high risk (fam/radiation hx)
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Pemberton's Maneuver
What does it test for?
How to perform it and positive result?
Nodular Thyroid Disease
Holding hands up for 2 minutes – thyroid traps large vessels and tracheal compression -will have venous compression/pooling – need to have surgery
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US for thyroid disease
gives an\_\_\_\_\_ information
Gives anatomic information
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Thyroid Cancer
(4) major types
(2) risk factors
More commonly seen in what gender, but worse prognosis in what gender?
(1) Cancer diagnosis seen in pts with underlying Hashimoto's
**Papillary\*, Follicular\*,** Medullary, Anaplastic
**Radiation exposure, Family History**
More commonly seen in women, but worse prognosis in men
Non-Hodgkin's Lymphoma (rare, rapidly enlarging neck mass)
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Papillary vs. Follicular Thyroid Cancer
(1) most common, (1) 2nd most common
**Mainstay of therapy (2) +/- (1)**
Follow serum __ as marker of disease
1. Papillary
1. Metastasis usually to (1), also to (2)
2. Prognosis
2. Follicular
1. (1) variant is more aggressive
2. Metastasis =
3. Prognosis
Papillary most common, Follicular 2nd most common
**Surgery is mainstay of therapy + RAI using I-131 +/- LT4 suppression**
**Serum Thyroglubulin (Tg)** - is the primary tumor biomarker used to detect recurrence
1. Papillary
1. Metastasis usually localized to neck lymph nodes, also to lung, bone
2. Excellent prognosis
2. Follicular
1. Hurthle cell (oncocytic) variant is more aggressive
2. Hematogenous spread - lung and bone
3. Slightly worse prognosis
*Note: If someone has thyroid Ca history – will probably see low thyroid levels bc want to suppress it to prevent more thyroid CA*
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Effect of COVID on Adrenal Axes?
No increased risk for adrenal insufficiency with COVID or being treated with dexamethasone during covid
