Endocrine Thyroid, Adrenal, Osteoporosis Flashcards
Hypothyroidism
=
- Primary Hypothyroidism =
- Secondary Hypothyroidism =
A clinical condition of reduced or absent thyroid hormone production
- Primary Hypothyroidism = Primary hormone deficit = Low T4 with High TSH
- Secondary Hypothyroidism = Secondary hormone deficit = Low T4 with Low TSH (or inappropriately normal TSH)
Secondary hypothyroidism = pituitary or hypothalamus damage
Thyroid Testing
(1) = Master test - very sensitive, to be done with a measure of peripheral hormone…. (very useful EXCEPT if problem is central hypothyroidism)
(1)= unbound portion (most useful measure of biologically active hormone in most circumstances)
(1) = binding protein dependent (used in pregnancy)
(1) = sometimes useful for assessing thyroid dysfunction in acute illness
TSH = Master test - very sensitive, to be done with a measure of peripheral hormone…. (very useful EXCEPT if problem is central hypothyroidism)
Free T4 = unbound portion (most useful measure of biologically active hormone in most circumstances)
Total T4 = binding protein dependent (used in pregnancy)
Total T3 = sometimes useful for assessing thyroid dysfunction in acute illness
Tests of Autoimmunity
(4)
TPO
TgAb
TSI
TBII
Thyroid Imaging
(1) – assess for echogenicity, nodularity, vascularity
(1) – _____ anatomical testing (usually for _____thyroidism) helps differentiate thyroiditis, graves disease, toxic adenoma and toxic MNG as well as ”cold nodules”
Ultrasound – assess for echogenicity, nodularity, vascularity
Uptake and Scan – functional anatomical testing (usually for hyperthyroidism)helps differentiate thyroiditis, graves disease, toxic adenoma and toxic MNG as well as ”cold nodules”
Primary Hypothyroidism
(1) common autoimmune hypothyroid disease
Diagnosis (2) positive
Hashimotos Thyroid Disease
Autoimmune TPO antibodies (thyroperoxidase antibodies) + and TgAb (thyroglobulin antibodies)
Primary Hypothyroidism Etiology
- Iatrogenic
- Total _______
- ____ I131 therapy
- Cancer-related i______therapy*
- I_____ deficiency
- Infiltrative diseases
- External rad_______ for other disorders
- Inability to repair the gland after a thyroid____
- Medications
- Am_____
- L_____
- Con_______ (Dyshormonogenesis) (1/4000 births, screened at birth)
- Iatrogenic
- Total thyroidectomy
- RAI I131 therapy
- Cancer-related immunotherapy*
- Iodine deficiency
- Infiltrative diseases
- External radiation for other disorders
- Inability to repair the gland after a thyroiditis
- Medications
- Amiodarone
- Lithium
- Congenital (Dyshormonogenesis) (1/4000 births, screened at birth)
Secondary Hypothyroidism Etiology
- ________ disease
- T____
- Trauma
- Infiltrative disorders
- _____ based disease
- T_____
- Infiltrative disorders
- Radiation damage
- Surgery
- Sh________ syndrome
*More prevalent as ______ inhibitors become standard of care for several cancer types (ie Pembrolizumab, Nivolumab)
- Hypothalamic disease
- Tumors
- Trauma
- Infiltrative disorders
- Pituitary based disease
- Tumors
- Infiltrative disorders
- Radiation damage
- Surgery
- Sheehan’s syndrome
*More prevalent as PdL-1 inhibitors become standard of care for several cancer types (ie Pembrolizumab, Nivolumab)
Hypothyroidism Symptoms
- ______ intolerance
- Proximal muscle _____ness
- F______ and listlessness
- Weight ____– usually with a poor appetite
- GI =
- ____ness– accumulated fluid in the vocal cords
- ______ mentation
- Menorrhagia, Irregular menses or _____hea
- __creased sweating
- Cold intolerance
- Proximal muscle weakness
- Fatigue and listlessness
- Weight gain – usually with a poor appetite
- Constipation
- Hoarseness – accumulated fluid in the vocal cords
- Slowed mentation
- Menorrhagia, Irregular menses or amenorrhea
- Decreased sweating
Hypothyroidism Physical Exam
- Skin moisture?
- Skin temperature?
- Periorbital _____ - GAGs
- De_____ affect
- _____tension (diastolic)
- _____cardia
- Decreased myocardial ______ (EKG changes)
- Le_____
- Ed____ (nonpitting)
- B_____ nails and hair
- Dry skin
- Cold skin
- Periorbital edema - GAGs
- Depressed affect
- Hypertension (diastolic)
- Bradycardia
- Decreased myocardial contractility (EKG changes)
- Lethargy
- Edema (nonpitting)
- Brittle nails and hair
Myxedema Coma
causes (2)
- VERY _____ (but life-threatening)
- Most people with profound hypothyroidism do NOT have myxedema coma
Infection, Injury
- VERY RARE (but life-threatening)
- Most people with profound hypothyroidism do NOT have myxedema coma
Hypothyroidism Treatment
Rx (1)
- High dose IV ___ and for myxedema coma ***IF CENTRAL HYPOTHYROIDISM IS SUSPECTED NEED TO GIVE WITH _____!!**
- 1.6 mcg/kg body weight administered orally = full replacement
- _____ replacement for at risk populations
- El______
- C___ or CAD equivalent patients (DM, etc.)
- Long half life – __ days
Levothyroxine – LT4
- High dose IV T4 and T3 for myxedema coma ***IF CENTRAL HYPOTHYROIDISM IS SUSPECTED NEED TO GIVE WITH STEROIDS!!**
- 1.6 mcg/kg body weight administered orally = full replacement
- Slow replacement for at risk populations
- Elderly
- CAD or CAD equivalent patients (DM, etc.)
- Long half life – 7 days
Subclinical Hypothyroidism
TSH =
FT4 =
- _________ whom to treat
- Most agree that one should treat if TSH >__ [normal <4.5 mIU/L]
- ALWAYS _____ a TSH and FT4 (especially if between 5-10)
- 30-40% _______ if followed
- TSH curve changes with age: TSH of 5.5 may be _____ in ones 80s
- You may otherwise be giving someone a lifetime of unneeded medication
TSH elevated
FT4 normal
- Controversial whom to treat
- Most agree that one should treat if TSH >10 [normal <4.5 mIU/L]
- ALWAYS repeat a TSH and FT4 (especially if between 5-10)
- 30-40% normalize if followed
- TSH curve changes with age: TSH of 5.5 may be normal in ones 80s
- You may otherwise be giving someone a lifetime of unneeded medication
- Generally, subclinical hypothyroidism is overtreated - potential to overmedicate with synthroid and potentiate afib and osteoporosis*
- the only time i am aggressive with treating subclinical hypothyroidism is in pregnancy bc fetus cannot make its own thyroid hormone - prevent miscarriage and malformation in baby - goal TSH of 1-2 especially if there is TPO antibodies*
Hypothyroidism Lab Parameters for Follow Up
When should you repeat labs after starting treatment or a dose change?
- Goal – Primary hypothyroidism =
- Goal – Secondary hypothyroidism =
Wait 6 weeks to repeat TFTs after any dose change
- Goal – Primary hypothyroidism – normal TSH and FT4
- Goal – Secondary hypothyroidism – mid-level of normal FT4 range
Hyperthyroidism
=
- Primary Hyperthyroidism =
- Secondary Hyperthyroidism =
A medical condition of excess thyroid hormone levels..
- Primary Hyperthyroidism = Primary Hormone Excess = High T4 with Low TSH
- Secondary Hyperthyroidism = Secondary Hormone Excess = High T4 with High TSH
Thyrotoxicosis Types
- (1) – autoimmune stimulation of the thyroid
- (1) (adenoma – Plummer’s disease)
- Toxic ___nodular goiter
- (1) – many types, release of preformed thyroid hormone from damage to the gland
- (1) (thyrotoxicosis factitia or iatrogenic)
Rare causes
- TSH producing p_____ adenoma
- (1) mediated hyperthyroidism in pregnancy
- Drugs – (1) or (1) administration (Jod-Basedow effect)
- Graves’ Hyperthyroidism – autoimmune stimulation of the thyroid
- Toxic nodule (adenoma – Plummer’s disease)
- Toxic multinodular goiter
- Thyroiditis – many types
- Excess levothyroxine administration (thyrotoxicosis factitia or iatrogenic)
Rare causes
- TSH producing pituitary adenoma
- HCG mediated hyperthyroidism in pregnancy
- Drugs – amiodarone or iodine administration (Jod-Basedow effect)
Hyperthyroidism Symptoms
- P________
- N_____ness
- Ag_____ or irritability
- ____ intolerance
- Tr_____
- Easy Fatigue
- Muscle ____kness
- Weight _____ with _____ appetite
- _____ or Double Vision
- GI =
- ____menorrhea
- Palpitations
- Nervousness
- Agitation or irritability
- Heat intolerance
- Tremor
- Easy Fatigue
- Muscle weakness
- Weight loss with good appetite
- Blurry or Double Vision
- Frequent bowel movements
- Oligomenorrhea (infrequent menstrual periods)
Hyperthyroidism Physical Exam
- G______
- _____ycardia (ST most commonly)
- Eye lid re_____
- Atrial arrhythmias – esp. (1)
- Skin moisture (1), temp (1)
- Proximal myopathy
- Gynecomastia (rare)
- Systolic _____– high output CHF
- ____ pulse pressure
- Goiter
- Tachycardia (ST most commonly)
- Eye lid retraction
- Atrial arrhythmias – esp. A Fib
- Warm, moist skin
- Proximal myopathy
- Gynecomastia (rare)
- Systolic Murmur – high output CHF
- Wide pulse pressure
Thyrotoxicosis-Consequences of Untreated Hyperthyroidism
- Atrial _____
- Sinus _____cardia
- (1) – High Output
- _____ pectoris
- O_____ and O______
- Thyroid _____
- D_____
- Atrial fibrillation
- Sinus tachycardia
- Congestive heart failure – High Output
- Angina pectoris
- Osteopenia and Osteoporosis
- Thyroid Storm
- Death
Hyperthyroidism
(1) Disease
60-80% of thyrotoxicosis. More common in females.
(3) antibodies
Graves Disease
- Thyroid Stimulating Immunoglobulin (TSI)* stimulates the TSH-Receptor and mimics the action of TSH
- TPO + in many cases also seen
- TBII – Thyroid Binding Imunoglobulin
Pathognomonic Findings in Graves Disease
- o______mopathy (cytokines)
- br____/th_____ in thyroid gland
- pretibial _______ (NOT that myxedema)
- ophthalmopathy (cytokines)
- bruit/thrill in thyroid gland
- pretibial myxedema (NOT that myxedema)
Graves Disease the Antibodies
- (1)
- Not so specific
- Very sensitive for auto-immune related thyroid disease
- Have a low threshold for ordering when considering any thyroid disease
- (1)
- Very specific
- Not so sensitive
- Can take a week for lab to result (depends upon your lab)
- (1)
- Can be an antagonist to the TSH-Receptor
- Can be the term used for a group of antibodies to the TSH-Rec
- Pretty specific for Graves’ disease
- Can come back within a day or as much as a week (depends upon lab)
- Anti-TPO – anti-peroxidase antibody
- Not so specific
- Very sensitive for auto-immune related thyroid disease
- Have a low threshold for ordering when considering any thyroid disease
- TSIg – Thyroid stimulating immunoglobulin*
- Very specific
- Not so sensitive
- Can take a week for lab to result (depends upon your lab)
- TBII – Thyrotropin binding inhibitory immunoglobulin (aka TRAb – Thyroid Receptor Ab)
- Can be an antagonist to the TSH-Receptor
- Can be the term used for a group of antibodies to the TSH-Rec
- Pretty specific for Graves’ disease
- Can come back within a day or as much as a week (depends upon lab)
Graves Disease - Infiltrative Ophthalmopathy
- Symptoms
- ___ness, dryness, itching
- _____tosis (only found in graves disease), Corneal exposure
- Ed____
- Bl____ vision or loss of vision
- Often times also need to bring in ophthal to help address eyes and potentially ______
- ymptoms
- Redness, dryness, itching
- Proptosis (only found in graves disease), Corneal exposure
- Edema
- Blurry vision or loss of vision
- Often times also need to bring in ophthal to help address eyes and potentially decompress
Thyrotoxicosis - Anatomic Imaging
(1) = identifies nodules, vascularity
(1) = helps differentiate cause of hyperthyroidism
Thyroid US = identifies nodules, vascularity
NM (nuclear medicine) Uptake and Scan = helps differentiate cause of hyperthyroidism
Thyroiditis
Many different forms of Thyroiditis - this pattern is most common course for any patient (independent of etiology)
- Subacute – painful - post-v____ (de Quervain), Giant cell or Granulomatous
- Acute thyroiditis – fluctuance, severe pain, fever, marked ____ rise – bacterial
- Painless (silent) thyroiditis – most common - post-_____ (TPO+)
- Drug induce - Am_____, IFN-α, _____ inhibitors (cancer therapy), post-iodinated contrast load, post-RAI-131 – usually painless
- Reidel thyroiditis – fibrosis (usually leads to hypothyroidism) which can invade local structures. Very firm gland. Usually painless
- Subacute – painful - post-viral (de Quervain), Giant cell or Granulomatous
- Acute thyroiditis – fluctuance, severe pain, fever, marked ESR rise – bacterial
- Painless (silent) thyroiditis – most common - post-partum (TPO+)
- Drug induce - Amiodarone, IFN-α, PdL-1 inhibitors (cancer therapy), post-iodinated contrast load, post-RAI-131 – usually painless
- Reidel thyroiditis – fibrosis (usually leads to hypothyroidism) which can invade local structures. Very firm gland. Usually painless
Hyperthyroidism
Treatment
Rx (2) first line therapy
Rx (1) for symptomatic relief
Methimazole, Propylthiouracil
Beta Blockers for symptomatic relief
Methimazole, Propylthiouracil (Thionamides)
MOA
SE (1)* precautions for high dose
PTU - 3rd most common cause of _____ toxicity by medication, rarely indicated
Only inhibits production of new hormone, does not interfere with pre-formed hormone release
Directly interferes with the first step in thyroid hormone biosynthesis in the thyroid gland.
AGRANULOCYTOSIS* precautions for high dose
PTU - 3rd most common cause of liver toxicity by medication, rarely indicated
Beta Blockers
in ____ doses, are the drugs of choice for ______ relief and suppression of ________
in high doses, are the drugs of choice for symptomatic relief and suppression of tachyarrhythmia
Thyroiditis Treatment
JUST TREAT SYMPTOMS
What should you use? (2)
What should you not use? why?
JUST TREAT SYMPTOMS
Beta Blockers and Pain medication PRN
Do not use thionamides (methimazole/PTU) because will only lengthen the hypothyroid phase and cause confusion in interpreting TFTs
Hyperthyroidism Treatment Definitive Therapy
- (1)– relatively safe, though some studies suggest small 2/2 cancer risk. May exacerbate exophthalmos.
-
(1)
- ____ thyroidectomy for Graves’ or TMNG
- ____thyroidectomy for toxic adenoma
- RAI – I-131 – relatively safe, though some studies suggest small 2/2 cancer risk. May exacerbate exophthalmos.
-
Surgery
- Total thyroidectomy for Graves’ or TMNG
- Hemithyroidectomy for toxic adenoma
Thyroid Storm/Thyrotoxic Crisis
- Precipitated by an acute (1) or (1)
- Increased risk in poorly treated or inadequately treated thyrotoxicosis
- Avoid point scoring systems - it is a _____ diagnosis!
- Patient presentation where it is almost assuredly NOT storm?
- Patient presentation of storm likely?
- High mortality from ______ causes
- These patients require the ICU
- Precipitated by an acute insult or illness
- Increased risk in poorly treated or 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 they are agitated, febrile and cannot take PO – treat as storm until proven otherwise
- High mortality from cardiovascular causes
- These patients require the ICU
Thyroid Storm Treatment Algorithm
(4) Rx
- 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 (avoids Jodbasedow effect)
- High dose steroids +/-
Thyroid Nodules and Cancer
Categories of Goiter
(3)
- May be ____ (excess thyroid hormone) or ____ (normal FT4/TSH)
- Thyroid nodules are more common with ___
- Prevalence of palpable thyroid nodules: 2-6%
- Prevalence on thyroid U/S: 19-35%
- CT, MRI imaging = increased detection of likely ____ nodules (____diagnosis)
Diffuse, Multinodular, Uninodular
- May be Toxic (excess thyroid hormone) or Non-toxic (normal FT4/TSH)
- Thyroid nodules are more common with age
- Prevalence of palpable thyroid nodules: 2-6%
- Prevalence on thyroid U/S: 19-35%
- CT, MRI imaging = increased detection of likely benign nodules (overdiagnosis)
Thyroid Nodules
-
_____ nodules require further evaluation for _____
- >__ cm nodules may need FNA (consult with endocrine for this as many don’t need biopsies)
- High risk individuals include…____ history and ____exposure
- Usually asymptomatic – but always need to monitor for symptoms
- Dysph____
- Dys____ with arms raised or lying down
- H____ness which does not resolve, Str____
-
Asymptomatic nodules require further evaluation for cancer
- >1 cm nodules may need FNA (consult with endocrine for this as many don’t need biopsies)
- High risk individuals include…Family history and Radiation exposure
- Usually asymptomatic – but always need to monitor for symptoms
- Dysphagia
- Dyspnea with arms raised or lying down
- Hoarseness which does not resolve, Stridor
Thyroid Cancer
(4) Major Types
One of a few cancers still increasing in prevalence (reasons not clear)
Which type has the worst prognosis?
What cancer (although rare) has been associated with Hashimoto’s?
- Papillary
- Follicular
- Medullary (more on this later….)
- Anaplastic (worst prognosis of ALL cancers) – Rapid enlarging neck mass – requires urgent referral for core biopsy to consider new treatment modalities
Non-Hodgkins Lymphoma seen in underlying Hashimoto’s - rare, usually rapid enlarging neck mass that requires urgent referral for core biopsy, refer to oncology if lymphoma
Thyroid Cancer Risk Factors
- R_____ exposure
- F______ history
- More commonly seen in what gender? but worse prognosis in what gender?
- Radiation exposure
- Family history
- More commonly seen in woman, but worse prognosis in men
Mainstay = surgery + radioactive iodine after surgery (has changed a bit - if its not super high risk don’t want to give RI)
Papillary Thyroid Cancer
- ____ common
- ______ metastasis – neck lymph nodes
- Also spreads to lung and bone
- _____ Prognosis
- Responds to ____
- ____ is mainstay of therapy +/- RAI using I-131 + LT4 suppression
- Follow serum thyroglobulin as marker of disease
- Most common
- Lymphatic metastasis – neck lymph nodes
- Also spreads to lung and bone
- Excellent Prognosis
- Responds to I-131
- Surgery is mainstay of therapy +/- RAI using I-131 + LT4 suppression
- Follow serum thyroglobulin as marker of disease
Follicular Thyroid Cancer
- ____ most common
- _____ cell (oncocytic) variant is more aggressive
- _____ogenous spread – lung and bone
- _____is mainstay of therapy + ___using I-131 + LT4 suppression
- Follow serum Tg as marker of disease
- Associated with a slightly _____ prognosis
- 2nd most common
- Hurthle cell (oncocytic) variant is more aggressive
- Hematogenous spread – lung and bone
- Surgery is mainstay of therapy + RAI using I-131 + LT4 suppression
- Follow serum Tg as marker of disease
- Associated with a slightly worse prognosis
Primary Hyperaldosteronism
Aldosterone Mediated ______
- Prevalence of 5-10% within a general population
- Often mistaken for _____ hypertension and thus missed
-
Most pts with hyperaldosteronism are ____kalemic
- Only 9-37% have spontaneous _____kalemia (K <3.5mEq/L)
- Prevalence of 5-10% within a general population
- Often mistaken for essential hypertension and thus missed
-
Most pts with hyperaldosteronism are normokalemic
- Only 9-37% have spontaneous hypokalemia (K <3.5mEq/L)
Primary Hyperaldosteronism Screening
Hypertension with spontaneous?
- Severe hypertension (>___mmHg systolic or >___ mmHg diastolic)
- _-_ or more antihypertensives
- Hypertension with adrenal incidentaloma
- Hypertension and FHx of?
- Hypertension + Family hx of known C_____ Syndrome
Hypertension with spontaneous hypokalemia or low dose diuretic-induced hypokalemia
- Severe hypertension (>160 mmHg systolic or >100 mmHg diastolic)
- 2-3 or more antihypertensives
- Hypertension with adrenal incidentaloma
- Hypertension and FHx of HTN/CVA at a young age (<40 years) – Hypertension + Family hx of known Conn’s Syndrome
Primary Hyperaldosteronism Screening Misconceptions
- “My patient is too ___ to have PA” – Avg age of diagnosis 49 (+/- 7)
- “My patient’s potassium is ____ so can’t have PA” – Up to 90% have normal potassium
- “My patient is on an ARB or ACE so I would need to take them off these to test for PA” –?
- “My patient had a CT or MRI and it didn’t show an adrenal nodule so they can’t have PA” –?
- “Why would I look for this – its such an uncommon problem” – Up to __% of all hypertension is due to primary hyperaldosteronism
- “My patient is too old to have PA” – Avg age of diagnosis 49 (+/- 7)
- “My patient’s potassium is normal so can’t have PA” – Up to 90% have normal potassium
- “My patient is on an ARB or ACE so I would need to take them off these to test for PA” –Patients can be screened on these agents. We can worry about the “grey area”
- “My patient had a CT or MRI and it didn’t show an adrenal nodule so they can’t have PA” – 42% masses <6mm so can’t be seen on CT (CT does not rule out hyperaldo)
- “Why would I look for this – its such an uncommon problem” – Up to 10% of all hypertension is due to primary hyperaldosteronism
Primary Hyperaldosteronism Screening
- Check (3) labs? when?
- What are normal plasma aldosterone and renin levels?
- What Aldosterone/Renin ratio is diagnostic of primary aldosteronism? If it is suspicious, what should you do?
- Check aldosterone, plasma renin (PRA), and chem-7 for potassium
- Aldosterone 7-30 ng/dL, Plasma normally less than 1 (0.7-3.3 ng/ml/hr)
- High Aldosterone/Renin Ratio (ARR) is diagnostic - >25 (20-30 is ambiguous - send to endocrine/renal within this range)
Primary Hyperaldosteronism Take Away Message
- Adrenal Hypertension is ___ rare
- If it isn’t identified by the primary care physician it can lead to serious complications even IF blood pressure is controlled
- Screening is ____ and should be done for patients
- The hard part (confirmatory testing, imaging localizing studies with adrenal venous sampling) can be done by a _____
- Tx = ______
- Adrenal Hypertension is NOT rare
- If it isn’t identified by the primary care physician it can lead to serious complications even IF blood pressure is controlled
- Screening is easy and should be done for patients
- The hard part (confirmatory testing, imaging localizing studies with adrenal venous sampling) can be done by a specialist
- Tx = spironolactone
Primary Adrenal Insufficiency
=
- The adrenal medulla is usually ____
- Must be __lateral and involve destruction of __% of the gland before one develops signs/symptoms
Destruction of the mineralocorticoid, glucocorticoid, androgen producing capabilities of the adrenal cortex
- The adrenal medulla is usually intact
- Must be bilateral and involve destruction of 90% of the gland before one develops signs/symptoms
Primary Adrenal Insufficiency
ACTH levels =
Mineralocorticoid levels =
ACTH levels = Excess ACTH (negative feedback)
Mineralocorticoid levels = Mineralocorticoid deficiency
Primary Adrenal Insufficiency Etiology
-
(1) adrenalitis (most common in USA)
- May be associated with autoimmune polyglandular syndrome I or II
- ______ adrenalitis
- Tuberculosis (most common in developing world)
- HIV and associated opportunistic infections
- Fungal infections
- Bacterial – meningococcus (Waterhouse-Friedrichson syndrome)
- Cancer ______
- Carcinoma of lung, renal and breast
- H_____ or thr______
- Sepsis
- Warfarin mediated
- Anti-phospholipid syndrome
- Rarely – d____ (ketoconazole), CAH, adrenoleukodystrophy
- Auto-immune adrenalitis (most common in USA)
- May be associated with autoimmune polyglandular syndrome I or II
- Infectious adrenalitis
- Tuberculosis (most common in developing world)
- HIV and associated opportunistic infections
- Fungal infections
- Bacterial – meningococcus (Waterhouse-Friedrichson syndrome)
- Cancer metastases
- Carcinoma of lung, renal and breast
- Hemorrhage or thrombosis
- Sepsis
- Warfarin mediated
- Anti-phospholipid syndrome
- Rarely – drugs (ketoconazole), CAH, adrenoleukodystrophy
Secondary Adrenal Insufficiency
=
What happens overtime?
Interruption of the hypothalamic-anterior pituitary axis such that a deficit in cortisol production occurs, may be hypothalamic or pituitary in origin
Over time, the lack of ACTH stimulation of the adrenal causes atrophy of the adrenal gland
Secondary Adrenal Insufficiency
CRH/ACTH levels =
Mineralocorticoid levels =
Deficiency in CRH or ACTH
Mineralocorticoid intact
Main difference is glomerulosa that makes aldosterone remains intact in secondary AI
Secondary Adrenal Insufficiency Etiology
Most common cause (1)
Any cause of (1)
Exogenous Glucocorticoid administration (most common)
(Oral, systemic or inhaled, Duration and dose plays a role)
- Any cause of hypopituitarism
- Tumors, radiation, pituitary surgery
- Infiltrative diseases: sarcoid, TB, histiocytosis X
- Lymphocytic hypophysitis: autoimmune, pregnant woman
- Postpartum pituitary necrosis (Sheehan’s syndrome)
- Head trauma
AI Non-Specific Symptoms
- F_____, listlessness, fever, abdominal pain, nausea, poor appetite, emesis, generalized weakness, dizziness
- Sexual dysfunction, loss of ____
- Weight ____
- blood pressure =
- Fatigue, listlessness, fever, abdominal pain, nausea, poor appetite, emesis, generalized weakness, dizziness
- Sexual dysfunction, loss of libido
- Weight loss
- Orthostatic hypotension
Specific Primary AI Manifestations
(1) from increased ACTH stimulation
(1) from absence of aldosterone
Skin pigmentation from increased ACTH stimulation
Salt craving from absence of aldosterone
(skin pigmentation from increased melanin on palms, dorsal surface of hands, buccal mucosa, sun-exposed areas)
Secondary AI Manifestations
(think hypopituitarism)
- ____ dysfunction, loss of ____
- Loss of sexual h____
- Diabetes ____ (polyuria, increased thirst)
- Head____
- _____ field deficits
- Sexual dysfunction, loss of libido
- Loss of sexual hair
- Diabetes insipidus (polyuria, increased thirst)
- Headache
- Visual field deficits
Adrenal Insufficiency: Clinical Features
- Na =
- K and pH =
- Glucose =
- BP =
- WBC =
- Hyponatremia
- Cortisol deficiency
- Cortisol required for free water excretion
- Cortisol suppresses ADH release
- Aldosterone deficiency (salt wasting) in primary AI
- Cortisol deficiency
- Hyperkalemia and metabolic acidosis
- Specific to primary AI (aldosterone deficiency)
- Hypoglycemia
- Hypotension
- Salt wasting with concomitant volume depletion (primary AI)
- Inability to maintain vascular tone (cortisol deficiency)
- Eosinophilia
Diagnosis of Adrenal Insufficiency
(2)
Which test do you use to find out if patient has primary vs. secondary AI?
Basal 8 AM Cortisol and ACTH
Synthetic ACTH (Cosyntropin Stimulation Test)
ACTH stimulation testing to establish level of defect (primary vs. secondary)
Basal 8 AM Cortisol and ACTH
Cortisol levels that rule in and out AI?
ACTH levels that rule in and out AI?
Cortisol levels <3 = 100% specific, Cortisol levels >15 rules out AI
ACTH levels >100 = primary AI, ACTH levels variable in secondary AI
Cosyntropin Stimulation Test (Synthetic ACTH)
Most common test? What result rules out AI?
Whom to test?
Most common test: 250mcg short (60 minutes) stimulation
Cortisol >15 mcg/dL after 60 min rules out AI (unless evaluating for acute pituitary injury)
Patients with indeterminate basal cortisol levels, All patients for whom time is of the essence
Primary AI Treatment
What should you replace? Using what?
Replace Glucocorticoids and Mineralocorticoids
Glucocorticoid replacement using Hydrocortisone, Dexamethasone, Prednisone
Mineralocorticoid replacement using Fludrocortisone
Secondary AI Treatment
What do you replace?
Only need glucocorticoid replacement, because remember glomerulosa that makes aldosterone remains intact in secondary AI
AI Home Precautions
- (1) bracelet
- Steroid _____ injection kit
- ____ or _____ dose “___ day” rules
- If unable to take oral pills?
- Medic-alert bracelet
- Steroid emergency injection kit
- Double or triple dose “sick day” rules
- If unable to take oral pills - call for emergency assistance
Acute Adrenal Crisis
Clinical manifestations
- ____tension followed by ____(refractory to IVF/Rx)
- ____glycemia
- A______ pain and emesis
- BP =
- ____natremia and ____glycemia
- F____
- Hypotension followed by shock (refractory to IVF/Rx)
- Hypoglycemia
- Abdominal pain and emesis
- Orthostatic hypotension
- Hyponatremia and hypoglycemia
- Fever
Acute Adrenal Crisis
Diagnosis =
Treatment =
Diagnosis = Random cortisol +/- cosyntropin stimulation testing (often, one can’t wait for cosyntropin stimulation – if unstable – treat)
Treatment = Hydrocortisone 100 mg IV every 8 hours, Supportive treatment, IVF, Treat underlying illness
Calcium and Bone Metabolism
(3)
Hypocalcemia
Hypercalcemia
Osteoporosis
Hypocalcemia Clinical Manifestations
Neurologic:
- ____ness, t_____, irritability, ____ reflexes, ____ sign, s_____ (basal ganglia calcification)
Musculoskeletal:
- Muscle cr_____, ______ sign (carpopedal spasm), laryngospasm, bronchospasm, tet____
Cardiac:
- (1) (can induce Torsades if severe enough), CHF
Neurologic:
- Numbness, tingling, irritability, brisk reflexes, Chvostek’s sign, seizures (basal ganglia calcification)
Musculoskeletal:
- Muscle cramps, Trousseau’s (carpopedal spasm), laryngospasm, bronchospasm, tetany
Cardiac:
- long QT (can induce Torsades if severe enough), CHF
- Chvostek’s sign = t**witch of the facial muscles that occurs when gently tapping an individual’s cheek, in front of the ear*
- Trousseau’s sign refers to the* involuntary contraction of the muscles in the hand and wrist (i.e., carpopedal spasm) that occurs after the compression of the upper arm with a blood pressure cuff.
Hypercalcemia Clinical Manifestations
Neurologic:
- Poor c______, f____, weakness, poor m____, depression, con____, co__
Gastrointestinal:
- Con_____, anorexia, n____, v_______, panc_____, peptic _____
Renal:
- ____uria, _____dipsia, dehydration, nephro______, nephrocalcinosis
Cardiac:
- palp_____, arrh_____, bradycardia, ____ QT, AV block
- “vicious cycle” of severe hypercalcemia- renal/GI (polyuria/nausea/vomiting->dehydration- >increased Ca++)
Neurologic:
- Poor concentration, fatigue, weakness, poor memory, depression, confusion, coma
Gastrointestinal:
- Constipation, anorexia, nausea, vomiting, pancreatitis, peptic ulcers
Renal:
- Polyuria, polydipsia, dehydration, nephrolithiasis, nephrocalcinosis
Cardiac:
- palpitations, arrhythmia, bradycardia, short QT, AV block
- “vicious cycle” of severe hypercalcemia- renal/GI (polyuria/nausea/vomiting->dehydration- >increased Ca++)
Hypocalcemia: Differential Dx
(1): (PTH↓Ca↓)
- Auto_____
- Congenital
- Post_____ (most common)
- ______ deficiency (severe)
- Neck irr_______
- Infiltrative
- Neonatal
- _____-bone syndrome (post Parathyroidectomy)
Hypoparathyroid: (PTH↓Ca↓)
- Autoimmune
- Congenital
- Postsurgical (most common)
- Magnesium deficiency (severe)
- Neck irradiation
- Infiltrative
- Neonatal
- Hungry-bone syndrome (post Parathyroidectomy)
Hypocalcemia: Differential Dx
(1): (PTH ↑Ca↓)
- (1) deficiency
- Hypo______
- PTH re_____
- Vitamin D re_______
- Medications
- Anti-_____ treatment
- Pancreatitis
- Acute critical illness
- Acute rh________
- Tumor _____
- Multiple transfusions/plasmapheresis
Non-hypoparathyroid: (PTH ↑Ca↓)
- Vitamin D deficiency
- Hypocalcemia
- PTH resistance
- Vitamin D resistance
- Medications
- Anti-neoplastic treatment
- Pancreatitis
- Acute critical illness
- Acute rhabdomyolysis
- Tumor lysis
- Multiple transfusions/plasmapheresis
Hypocalcemia Diagnosis and Treatment
Diagnostic Labs (3)
Treatment Rx (4)
Measure Calcium, PTH, and Mag level
Depends on etiology, calcium po or iv (if symptomatic or severe may need iv infusion), calcitriol (vitamin D), mag repletion, resolve underlying issue. rhPTH
Hypercalcemia Diff Dx
____ mediated (PTH ↑ Ca ↑)
- (1) (PTH mediated)
PTH mediated (PTH ↑ Ca ↑)
- Primary Hyperparathyroidism (PTH mediated)
Hypercalcemia Diff Dx
_____ mediated (PTH ↓ Ca ↑)
- M______ (non-PTH mediated) (humoral, lytic, vitD and/or cytokine production)
- Thyro______
- Granulomatous disease – aka – T__, Sarcoidosis
- ____-induced (Li (can be PTH mediated), Th______
- Vitamin D ____, Calcitriol ____
- Imm______
Non-PTH mediated (PTH ↓ Ca ↑)
- Malignancy (non-PTH mediated) (humoral, lytic, vitD and/or cytokine production)
- Thyrotoxicosis
- Granulomatous disease – aka – Tb, Sarcoidosis
- Drug-induced (Li (can be PTH mediated), Thiazides
- Vitamin D Excess, Calcitriol excess
- Immobilization
Hypercalcemia Diff Dx.
_____Area (PTH ↑ Ca ↔)
- _____calcemic ____parathyroidism
- _____ Hypocalciuric Hypercalcemia (FHH)
- Id_____ hypercalciuria
Grey Area (PTH ↑ Ca ↔)
- Normocalcemic hyperparathyroidism
- Familial Hypocalciuric Hypercalcemia (FHH)
- Idiopathic hypercalciuria
Hypercalcemia Diagnosis and Treatment
What labs to check?
Treatment
- h______
- di______
- bis_______
- “specific” (_____ for hyperpara; _______ for VitD tox and granulomatous; Rx CA)
Check PTH - to see if PTH mediated vs. non-mediated
Treatment
- hydration
- diuretics
- bisphosphonates
- “specific” (surgery for hyperpara; glucocorticoids for VitD tox and granulomatous; Rx CA)
Primary Hyperparathyroidism
Surgery is recommended if: Ca ↑ ____, Ost______, recurrent n________, age
- Localization techniques (only after dx established!) =
- Surgical approach: normally resection of __ (or rarely more than 1 PTH ____)
- Are you cured after surgery?
Medical Rx (if not a candidate for surgery) =
Surgery is recommended if: Ca ↑ 11.5, Osteoporosis, recurrent nephrolithiasis, age<50
- Localization techniques (only after dx established!)- US, sestamibi scan, 4D CT
- Surgical approach: normally resection of 1 (or rarely more than 1 PTH adenoma)
- Surgery offers cure
Medical Rx - cinacalcet (if not candidate for surgery), observation (if not severe)
Osteoporosis
Clinical Definition: Bone Strength = (1) + (1)
DEXA definition = T score > -2.5 SD below the mean for young adults
Clinical Definition: Bone Strength = Bone Density (easy to measure) + Bone quality (harder to measure)
DEXA definition = T score > -2.5 SD below the mean for young adults
Osteoporosis
Systemic skeletal disease characterized by
- Low bone ____→ degree of mineralization
- Low bone _____→ macroarchitecture, microarchitecture, microdamage accumulation, rate of bone turnover
- Consequently - there is an increase in bone fragility and risk of ______
- Low bone mass → degree of mineralization
- Low bone quality → macroarchitecture, microarchitecture, microdamage accumulation, rate of bone turnover
- Consequently - there is an increase in bone fragility and risk of fracture
Osteoporosis Fractures
- Each year 1.5 million osteoporosis-related fractures occur in US, including 325,000 hip fractures.
- After age 50, one of every 2 women and one out of every 5 men will suffer an osteoporotic fracture during their lifetime.
- One in 5 people with ___ fracture end up in a ____ home within one year; more than 50 percent never regain their baseline functional status.
- About 25% of women and 20% of men with a _____fracture, suffer another fracture within 5 years; most within the first year. “____ begets ____”
- Each year 1.5 million osteoporosis-related fractures occur in US, including 325,000 hip fractures.
- After age 50, one of every 2 women and one out of every 5 men will suffer an osteoporotic fracture during their lifetime.
- One in 5 people with hip fracture end up in a nursing home within one year; more than 50 percent never regain their baseline functional status.
- About 25% of women and 20% of men with a fragility fracture, suffer another fracture within 5 years; most within the first year. “Fracture begets fracture”
Metabolic Bone Disease
Peak Bone Mass and Rate of Bone Loss
Intrinsic Factors
- G______, ___pathway
Extrinsic Factors
- Es____ Status
- XRC/Nut_____
- To_____
- C____/Vitamin __ status
- Chronic Diseases
- Medications
Intrinsic Factors
- Genes, wnt pathway
Extrinsic Factors
- Estrogen Status
- XRC/Nutrition
- Tobacco
- Calcium/Vitamin D status
- Chronic Diseases
- Medications
The Wnt signaling pathway is an ancient and evolutionarily conserved pathway that regulates crucial aspects of cell fate determination, cell migration, cell polarity, neural patterning and organogenesis during embryonic development**.
Systemic Diseases Associated with Osteoporosis
Endocrine =
Nutritional Disorders =
Medications =
Oncologic =
Inflammatory Arthritis =
Endocrine = Hypogonadism, Hyperprolactinemia, Hyperthyroidism, Cushing’s syndrome, Hyperparathyroidism
Nutritional Disorders = Malabsorption (Celiac sprue, Post-Gastrectomy, Pernicious Anemia
Medications = Glucocorticoids, Thyroxine, Anticonvulsants, GnRH, EtOH, Lithium, Heparin, Cyclosporine, Proton Pump Inhibitors, Thiazolidinediones
Oncologic = Multiple Myeloma (SPEP, UPEP)
Inflammatory Arthritis = Ankylosing Spondylitis, Rheumatoid Arthritis
Osteoporosis Treatment Lifestyle Measures
- Adequate (1) exercise (e.g., walking, moderate resistance training)
- ______ cessation
- Avoidance of excessive ______ intake (no more than ___ drinks/day)
- (1) Supplementation, dose
- (1) Supplementation, dose, target
- Adequate weight bearing exercise (e.g., walking, moderate resistance training)
- Smoking cessation
- Avoidance of excessive alcohol intake (no more than 2 drinks/day)
- Calcium Supplementation to a total intake of 1200-1500 mg/day for postmenopausal women and for men over 65 yo
- Vitamin D supplementation (400-800 IU/day) to achieve a serum 25-hydroxyvitamin D concentration >30 ng/mL*
Antifracture Pharm Therapy
Antifracture Pharm Therapy
Effect of osteoporosis therapy after a fragility fracture?
Anti-Osteoporotic Therapy After Fragility Fracture Lowers Rate of Subsequent Fracture
- All patients 50 and older who sustained a fragility fracture
- Treatment group: received anti-resorptive within 6 month with possession ration >80%
- No treatment group
- Outcome: 3 year rate of subsequent fracture
