Endocrine Flashcards
Toxic Thyroid Adenoma
The hyperplastic thyroid cells autonomously produce thyroid hormone without TSH
Neonatal thyrotoxicosis
Got it from her mama (Graves Dz)
Transplacental anti-TSHr Ab
Self-resolves in 3 months (when maternal Ab is gone)
In the meantime, give methimazole & beta blocker
PTH-Independent Hypercalcemia
Malignancy
Vitamin D Toxicity
Extrarenal conversion of 25-hydroxyVitD to 1,25 (Sarcoid)
PTH-Dependent Hypercalcemia
Primary Hyperparathyroidism
Familial Hypocalicuric Hypercalcemia
Lithium
Why do Addison’s patients get hyperpigmentation?
Cosecretion of Melanocyte-stimulating hormone with ACTH
Why do Addison’s patients get vitiligo?
Autoimmune destruction of melanocytes
Hyponatremia in endocrine patient
Addison’s
Pubertal gynecomastia treatment
Reassurance
Resolves in most patients within a few months to 2 years
Werdnig-Hoffman Syndrome
AR Disorder
Degeneration of anterior horn cells & cranial nerve motor nuclei. Floppy Baby (but not botulism)
Baby appears normal at first
Weeks later, develops: Apathy Weakness Hypotonia Large tongue Umbilical hernia
Congenital hypothyroidism
Familial or sporadic
Most commonly thyroid dysgenesis (Aplasia, hypoplasia or ectopic gland)
Elderly patient has severe thyrotoxicosis
Before radioactive iodine, what do you give them?
Methimazole or PTU
Essentially debulk, since radioactive iodine will transiently worsen the hyperthyroidism
Main substrates for gluconeogenesis
Gluconeogenic amino acids (from breakdown of muscle)
Main ones: Alanine & Glutamine
Lactate (from anaerobic glycolysis)
Glycerol 3-phosphate (from triacylglycerol in adipose)
Precocious puberty
Development of secondary sex characteristics before the age of:
8 in girls
9 in boys
Central precocious puberty
FSH is high
LH is high
GnRH is activated
Peripheral precocious puberty
FSH is low
LH is low
Gonads or adrenals release excess sex hormones
Clinical features of PCOS
Oligo-ovulation
Clinical or biochemical hyperandrogenemia
Polycystic ovaries on imaging
No evidence of another diagnosis
Clinical features of nonclassic CAH (21-hydroxylase Deficiency)
Oligo-ovulation
Hyperandrogenemia
Increased 17-hydroxyprogesterone levels
Presents later than infancy (nonclassic)
Teens to twenties
Girls:
Acne
Irregular menses
Hirsutism
Boys:
Precocious puberty
Clinical features of Ovarian/Adrenal tumors
Older age
Rapidly progressive symptoms
Increased androgen levels (>3x normal level)
Hyperprolactinemia
Amenorrhea
Galactorrhea
Increased prolactin levels
Cushing Syndrome
Cushingoid features (moon facies, buffalo hump)
Nonsuppressible dexamethasone suppression test
Increasd 24h urinary free cortisol
Acromegaly
Excessive growth
Increased GH
Increased IGF-1
Pathophys of 21-hydroxylase deficiency
Neither cortisol nor aldosterone are made
Pituitary increases ACTH to rectify low levels of cortisol
Adrenals undergo hyperplasia
Build-up of 17-hydroxyprogesterone is diverted to androgen synthesis
Meanwhile, aldosterone deficiency causes salt wasting, though hyponatremia is variable
Additionally, androgen excess impairs hypothalamic sensitivity to progesterone
Rapid GNrH secretion
Hypersecretion of LH & FSH
Increased gonadal steroid production
Most common thyroid epithelial malignancy
Papillary Thyroid Cancer
Second place is Follicular Thyroid Cancer
Follicular Thyroid Cancer
Peak incidence age 40 - 60
Firm thyroid nodule (Cold on scintigraphy)
Often discovered incidentally
FNA of suspected Follicular Thyroid Cancer
Useless
Cytologic findings are indistinguishable between follicular thyroid cancer and benign follicular adenomas
How do we tell the difference between Follicular Thyroid Cancer or Benign Follicular Adenomas?
Follicular Thyroid Cancer invades the tumor capsule and/or blood vessels
This is a finding on examination AFTER excision
How does Follicular Thyroid Cancer metastasize?
Hematogenously to distant tissues
Bone
Lung
Serum calcitonin elevation
Medullary Thyroid Carcinoma
Secreted by the parafollicular cells of the thyroid
MEN2
Path findings of Papillary Thyroid Cancer
Large cells
Ground glass cytoplasm
Pale nuclei w/ inclusion bodies & central grooving
Grainy, lamellated calcifications (Psammoma Bodies)
Hurthle Cells
Large polygonal cells
Eosinophilic cytoplasm
Large quantities of mitochondria
Seen in Follicular Thyroid Cancer
Also seen in Benign Thyroid Adenomas
Also seen in Hashimoto’s Thyroiditis
Patient presents with hyperthyroid symptoms
Undergoes contrast CT
Develops delirium, GI upset, agitation or seizure
Thyroid storm. The Iodinated contrast agent induced it!
What can trigger thyroid storm?
Iodine overload Surgery Trauma Infection Childbirth
What can thyroid storm lead to?
Cardiac arrhythmias CHF Seizures Hypotension Shock
Metabolic Syndrome
Hypertension
Impaired fasting glucose
Dyslipidemia
Overweight w/ central fat distribution (increased waist-to-hip ratio)
Steroids have been suppressing a patient’s HPA Axis
The patient discontinues the steroids
How long does it take for them to start secreting CRH & ACTH again?
6 - 12 months
Cortisol and ACTH levels in Central adrenal insufficiency
Morning:
Cortisol Low
ACTH Low
Aldosterone Normal
Cortisol and ACTH levels in Primary adrenal insufficiency
Morning:
Cortisol Low
ACTH High
Aldosterone Low
In DKA, why are potassium levels often high?
Extracellular shift of K (driven by plasma tonicity)
Loss of insulin-dependent potassium uptake
Hyperkalemia results despite total body potassium deficit
Why does DKA result in a total body potassium deficit?
Potassium loss in the urine (glucose-induced osmotic diuresis)
Renal elimination of potassium ketoacid salts
When you give insulin to a DKA patient, how do you avoid hypokalemia?
Monitor potassium closely
Add potassium to IV fluids once serum K < 5.2
Severe (often) Refractory Hypotension
Vomiting
Abdominal Pain
Fever
Adrenal crisis
Primary or due to suppression with steroid use
Treat with hydrocortisone or dexamethasone & aggressive fluid support
Do not wait for lab confirmation
In a patient receiving >20mg/day of prednisone, how soon do you see HPA suppression?
3 weeks
Increase doses of glucocorticoids during acute stressors (like surgery). They won’t naturally upregulate, so you have to give a “stress dose”
In a patient receiving 5 - 20mg/day of prednisone, how bad is their HPA suppression?
Variable
Pre-op evaluation with early-morning cortisol level is necessary to determine risk
Hypercalcemia of Thiazide use
Mild (<12mg/dL)
Rarely symptomatic
Difference between hypercalcemia of malignancy & primary hyperparathyroidism
Malignancy = Severe & Rapid Onset
Primary Hyperparathyroid = Gradual increase
How does sarcoidosis lead to hypercalcemia?
Extrarenal production of 1,25-dihydroxyvitamin D
Associated with hyperphosphatemia
Hypercalcemia with normal phosphorous
Osteolytic malignancies (Breast Cx, MM)
MEN1
Primary Hyperparathyroidism (Hypercalcemia) Pituitary tumors (Prolactin, visual defects) Pancreatic tumors (Gastrinoma)
MEN2A
Medullary Thyroid Cancer (Calcitonin)
Pheochromocytoma
Parathyroid hyperplasia
MEN2B
Medullary Thyroid Cancer
Pheochromocytoma
Mucosal neuromas / Marfanoid habitus
Patient needs a thyroidectomy and their mama died on the table during the exact same procedure.
Other than thyroid storm, what are you worried about?
MEN2A or MEN2B
A pheochromocytoma can be asymptomatic at time of diagnosis, but cause fatal intraoperative hypertension
What tests should every patient with medullary thyroid cancer get?
Plasma metanephrine assy
RET mutation testing (Chromosome 10)
We’re looking for MEN2A or MEN2B cuz pheos suck, especially during surgery
What is Medullary Thyroid Cancer?
Calcitonin-producing tumor
Parafollicular C cells in Thyroid
Oft associated with Pheochromocytoma as part of MEN2A or MEN2B
Patient with hyperinsulinism, but low insulin & C-peptide levels
Non-beta cell mesenchymal tumor
Secretes IGF II
Measure serum IGF II for diagnosis
If not, then they are injecting themselves
Necrotic migratory erythema
Elevated blood glucose levels
Glucagonoma
Differentiating Solfonylurea use from Beta Cell Tumor
Sulfonylurea Use - Proinsulin level often <20% of insulin
Confirm with serum levels of sulfonylurea
Patient with primary hyperaldosteronism is given a diuretic. What do we worry about?
Diuretic-induced hypokalemia
Oft do not have peripheral edema due to spontaneous diuresis (aldosterone escape)
Screening test for primary hyperaldosteronism
Early morning:
Plasma Aldosterone Concentration
Plasma Renin Activity
Primary Hyperaldo:
Ratio > 20
Plasma Aldosterone > 20
You can only do this test after drugs that alter this ratio (potassium-sparing diuretics) are held for 4 weeks
What drugs alter the Aldosterone/Renin Activity ratio?
Spironolactone
Eplerenone
Amiloride
Triamterene
Hold these for 4 weeks before attempting to measure the ratio.
Confirmation test for primary hyperaldosteronism
Salt loading
Document inability to suppress serum aldosterone
Then, abdominal CT
Most sensitive test for differentiating adrenal adenoma vs bilateral adrenal hyperplasia (in the absence of a discrete unilateral adrenal mass on imaging)
Adrenal venous sampling
Paraneoplastic syndromes from lung cancer
SIADH
Lambert-Eaton
Treatment for thyroid storm
Beta Blockers (propranolol) for symptoms
Thionamides (PTU) to block new synthesis
Iodine solution to block release of existing hormone
Give the iodine at least 1h after PTU, to present excess incorporation of iodine into thyroid hormone
Glucocorticoids to decrease peripheral conversion of T4 to T3
Amenorrhea with increased TSH
Hypothyroidism
Amenorrhea with increased Prolactin
Hyperprolactinemia
Amenorrhea with increased LH
Premature ovarian failure
Most feared side effect of PTU and Methimazole
Agranulocytosis
Occurs within 90 days of treatment
Patient complains of fever and sore throat shortly after beginning treatment
Discontinue the antithyroid agent
Measure WBC
If WBC < 1, discontinue the drug & give a broad spectrum antibiotic with pseudomonal coverage
If WBC <1.5, it probably isn’t the drug causing it
Routine WBC testing to monitor is not cost effective
What serum level of prolactin is diagnostic of a prolactinoma
> 200 ng/mL
Calculate Corrected Calcium
Measured Calcium + 0.8 (4 - serum albumin)
Low albumin will lower the measured calcium incorrectly
Prokinetic agents (GI)
Metoclopramide
Erythromycin
Cisapride
Metabolic abnormalities from hypothyroidism
Hyperlipidemia
Hyponatremia
Asymptomatic CK elevations (<10x normal)
Asymptomatic serum transaminase elevations
Hyperlipidemia of hypothyroidism
Either cholesterol alone (due to decreased LDL surface receptors and/or decreased LDL receptor activity) or both cholesterol and triglycerides (due to decreased lipoprotein lipase activity)
May take months to resolve despite adequate treatment of hypothyroidism
Statins increase risk of myopathy in poorly-controlled hypothyroidism. Give with caution in these patients.
Mechanism of hyponatremia in hypothyroidism
Decreased free water clearance
Anemia of hypothyroidism
Normocytic
Normochromic (due to decreased RBC Mass)
Anemia of chronic autoimmune thyroiditis
Pernicious anemia
Some can have macrocytosis without megaloblastic anemia
Preferred initial therapy for primary hyperaldosteronism (nonsurgical)
Spironolactone
However, it is a progesterone and androgen receptor antagonist. Decreased libido & gynecomastia in men. Breast tenderness, menstrual irregularities in women.
Eplerenone is a very selective mineralocorticoid antagonist without these side effects, and is alternate therapy.
Common side effects of pregabalin
Drowsiness
Weight Gain
Fluid Retention
Initial treatment for diabetic neuropathy
Tricyclics (Amitriptylline) - Avoid in patients > 65 for anticholinergic effects, avoid in patients with pre-existing cardiac disease due to conduction abnormalities Dual SSRIs (duloxetine) Anticonvulsants (Pregabalin, Gabapentin)
Indication for FNA of thyroid nodule
Normal or high TSH
Cold nodules
Thyroid cancer family history
Suspicious thyroid ultrasound findings
Indication for radionuclide scan of thyroid nodule
Low TSH
Hot nodules are almost always benign, can be treated for hyperthyroidism
What is the most common cause of Primary Adrenal Insufficiency in developed countries?
Autoimmune Adrenalitis
Can occur in isolation or in association with other autoimmune syndromes (hypothyroidism, vitiligo)
Key differences between Primary Adrenal Insufficiency and Central Adrenal Insufficiency
Primary has hyperpigmentation & hyperkalemia
Who should be screened for diabetes?
BP > 135/80
All patients >= 45 years
Anyone with BMI >25 & risk factors
Risk factors for diabetes in patients > 25
Physical inactivity First degree relative with diabetes High-risk race/ethnicity (nonwhite) Women whose birth weight >= 9 lb History of gestational DM Hypertension or prior cardiovascular disease Dyslipidemia (low HDL & high triglycerides) History of PCOS History of glucose intolerance
Screening tests for diabetes
Fasting plasma glucose
2h OGTT
HbA1C
How does pregnancy increase thyroid hormone production
Estrogen leads to increased Thyroxine Binding Globulin synthesis. More thyroxine is bound, so more is made.
hCG shares an alpha subunit with TSH, so stimulates TSH receptors
Management of pregnant patient with baseline hypothyroidism
Increase replacement thyroxine dose
Euthyroid sick syndrome
TFT changes in the setting of severe unrelated illness
Commonly:
Low total & free T3
Normal T4 & TSH
T4 & TSH may decrease further with continued illness.
Thyroid hormone supplementation not helpful
Subacute (Granulomatous or De Quervain’s) Thyroiditis
Hyperthyroidism
Suppressed TSH
Elevated ESR & CRP
Low radioiodine uptake
Follows acute viral illness
Associated with painful, tender goiter
DKA vs Hyperosmolar Hyperglycemic State
DKA: Type 1 Rapid Onset Hyperventilation & abdominal pain Anion gap metabolic acidosis Serum ketones Osmolality < 320
Hyperosmolar Hyperglycemic State: Type 2 Gradual onset Less hyperventilation & abdominal pain Normal anion gap, normal bicarb No (or small) serum ketones Osmolality > 320
Common precipitating factors for Hyperosmolar Hyperglycemic State in DMII patients
Infection Glucocorticoids Thiazides Pentamidine Atypical Antipsychotics Interruption of insulin therapy Trauma or acute illness (stroke, MI)
Subclinical hypothyroidism
Elevated TSH
Normal T4
T3 stays normal until late stages of hypothyroidism
Riedel’s (Fibrous) Thyroiditis
Inflammatory disorder
Fibrosclerosis of:
Thyroid
Surrounding Tissues
Often remote nonthyroidal structures (eg retroperitoneum)
Most patients have a hard goiter
Hypothyroidism (Subclinical or overt) may be seen
Manifestations of hypocalcemia
Perioral tingling/numbness Muscle cramps Tetany Carpopedal spasms Seizures QT Prolongation (sometimes)
If fall in calcium levels is rapid (like in surgical patients), a modest reduction can cause severe symptoms
Causes of Primary Hypoparathyroidism
Post-Surgical (most common)
Autoimmune
Congenital absence/maldevelopment of parathyroids (DiGeorge Syndrome)
Defective CaSR on parathyroids
Non-autoimmune destruction of parathyroids (Infiltrative diseases: Hemochromatosis, Wilson’s, Irradiation)
Most common nonsurgical cause of hypoparathyroidism
Autoimmune hypoparathyroidism
Drugs that cause Vitamin D deficiency by inducing P450 system
Phenytoin
Carbamazepine
Rifampin
Causes of calcium precipitation with phosphate in peripheral tissues
Renal Failure
Rhabdomyolysis
Phosphate Administration
Acute pancreatitis (calcium soaps in abdominal cavity)
Diffuse Osteoblastic Metastases (Prostate & Breast Cx)
Hypocalcemia & Hyperphosphatemia in the presence of normal renal function
Hypoparathyroidism
Most likely post-surgical or autoimmune
Non-autoimmune & Defective CaSR possible too
Necrolytic Migratory Erythema
Erythematous papules/plaques on face, perineum, extremities
Lesions enlarge & coalesce over 7 - 14 days
Central clearing, blistering, crusting, scaling at borders
Seen with glucagonoma
Glucagonoma Presentation
Necrolytic Migratory Erythema
Diabetes (easily controlled w/ oral agents & diet)
GI Symptoms
Weight Loss
Neuropsych (Ataxia, dementia, proximal weakness)
Association with venous throbmosis
Glucagonoma Diagnosis
Hyperglycemia
Glucagon > 500
Normocytic, normochromic anemia (either anemia of chronic disease or glucagon’s direct effect on erythropoiesis)
Abdominal imaging (CT or MRI) to localize tumor and/or metastases
Carcinoids
Slow-growing tumors in distal small intestine, proximal colon & lung
Secrete:
Histamine, serotonin, VIP
Where do carcinoids metastasize?
Liver
In these cases, the liver can’t metabolize the histamine, serotonin & VIP via first-pass metabolism. This leads to carcinoid syndrome
Carcinoid Syndrome
Flushing Secretory diarrhea Bronchospasm Cardiac valvular abnormalities Niacin Deficiency
Niacin Deficiency
Pellagra:
Dermatitis
Diarrhea
Dementia
Why does Carcinoid Syndrome lead to Niacin Deficiency?
Tryptophan is shunted to serotonin and none is left for niacin synthesis
Rapid-onset hirsutism (with or without virilization)
Androgen-secreting neoplasm (ovaries or adrenals)
Primary ovarian androgens
Testosterone
Androstenedione
Dehydroepiandrosterone
Primary adrenal androgens
Testosterone
Androstenedione
Dehydroepiandrosterone
Dehydroepiandrosterone-sulfate (DHEAS)
How can you tell the difference between ovarian or adrenal origin of an androgen-secreting neoplasm?
DHEAS is normal if the origin is ovarian
DHEAS is elevated if the origin is adrenal
Most common cause of short stature & pubertal delay in adolescents
Constitutional growth delay
Normal birth weight and height
From 6 months - 3 years, heigh growth velocity slows
3 years old, child develops normal velocity
Follows growth curve at 5th - 10th percentile
Bone age is delayed too
Puberty & adolescent growth spurt are delayed, but eventually occur.
Patient will reach normal adult height
Painless muscle weakness (progressive) Weight Gain Bone Loss Hypertension Hirsutism
Hypercortisolism (Cushing Syndrome)
Myopathy in Cushing Syndrome
Proximal weakness
Atrophy due to catabolic effects of cortisol on skeletal muscle
Hypercalcemia Symptoms
Abdominal Pain
Constipation
Polydipsia
Medications that increase the risk of Milk-Alkali Syndrome
Thiazide Diuretics
ACE Inhibitors
ARBs
NSAIDs
Milk-Alkali Syndrome
Hypercalcemia Hypophosphatemia Hypomagnesemia Metabolic Alkalosis AKI
Chronic Autoimmune (Hashimoto) Thyroiditis
Hypothyroid features
Diffuse goiter
TPO Antibody
Variable radioiodine uptake
Painless Thyroiditis
Variant of Hashimoto
Mild, brief hyperthyroid phase
Small, nontender goiter
Spontaneous recovery (also called silent thyroiditis)
TPO Antibody
Low radioiodine uptake
How does infection precipitate DKA?
Systemic release of insulin counterregulatory hormones (Catecholamines, Cortisol)
Excess glucagon causes hyperglycemia, ketonemia, osmotic diuresis
Renal net loss of potassium, but acidosis and decreased insulin activity leads to increased serum levels despite decreased total body stores
Mechanism of fatigue in hyperthyroidism
Chronic sympathetic hyperstimulation
Acute Thyrotoxic Myopathy
Severe Muscle Weakness (proximal or distal)
Without bulbar or respiratory muscle involvement
Weeks to months after onset of hyperthyroidism
Objective findings: Muscle atrophy
Treatment of hyperthyroidism improves the myopathy
Primary (Testicular) Hypogonadism in Men - Causes
Congenital (Klinefelter, Cryptorchidism)
Drugs (Alkylating Agents, Ketoconazole)
Orchitis (Mumps), trauma, torsion
Chronic kidney disease
Secondary (Pituitary/Hypothalamic) Hypogonadism in Men - Causes
Gonadotroph Damage: Tumor Cranial trauma Infiltrative diseases (hemochromatosis) Apoplexy
Gonadotroph Suppression: Exogenous androgens Hyperprolactinemia DM Morbid Obesity
Combined Primary/Secondary Hypogonadism in Men - Causes
Hypercortisolism
Cirrhosis
Low LH & Low Testosterone
Central Hypopituitarism
Low TSH & Low Thyroxine
Central Hypothyroidism
Central Hypopituitarism & Central Hypothyroidism
Nonfunctioning Pituitary Adenoma
Usually arises from gonadotropin-secreting cells (Gonadotrophs) in pituitary gland. These usually secrete LH & FSH, but now only secrete the common alpha-subunit (minimal clinical symptoms)
Ways Sheehan Syndrome can present
Failure of postpartum lactation
Secondary Adrenal Insufficiency (hypotension & anorexia)
Amenorrhea & Central Hypothyroidism
Management of Sheehan Syndrome
Replacement of deficient hormones
No effective treatment to restore lactation exists
Precocious Puberty with normal bone age
Isolated Breast Development - Premature Thelarche
Isolated Pubic Hair - Premature Adrenarche
Reassurance is appropriate
Ultrasound adrenals and ovaries/testes to look for source.
Precocious Puberty with advanced bone age
High LH - Central Precocious Puberty. Get a contrast MRI to rule out intracranial process. 80% of cases are idiopathic.
Low LH - Peripheral Precocious Puberty (Gonadotropin independent)
If the LH is not initially high, do a GnRH Stimulation test to determine the appropriate LH category.
Treatment for Idiopathic Gonadotropin Dependent (central) Precocious Puberty
GnRH Agonist Therapy (prevent premature epiphyseal plate fusion, maximize adult height potential)
Make sure you’ve done a contrast MRI first to rule out intracranial tumor. Treatment for that would usually be resection.
Danazol
Testosterone derivative
Progestin-like effects
Used in combination with GnRH agonists & progestins to treat endometriosis
Further evaluation for Gonadotropin Independent (peripheral) Precocious Puberty beyond a low LH
Ultrasound of adrenals, ovaries/testes to look for peripheral source
Untreated hyperthyroidism can lead to
Bone loss (Increased osteoclastic bone resorption)
Osteoporosis
Cardiac Tachyarrythmias
AFib
Does myopathy occur in hypothyroidism or hyperthyroidism?
Both!
Hypothyroid myopathy or Thyrotoxicosis
In hypothyroid myopathy, CK can be elevated for years before clinical symptoms of hypothyroid appear.
ESR/CRP may be normal
Manifestations of hypothyroid myopathy
Any of the above:
Asymptomatic CK Elevation Myalgias Muscle Hypertrophy Proximal Myopathy Rhabdomyolysis
Methimazole Adverse Effects
Agranulocytosis
1st Semester Teratogen
Cholestasis
PTU Adverse Effects
Hepatic Failure (Black Box Warning!) ANCA Vasculitis
Radioiodine Ablation Adverse Effects
Permanent Hypothyroidism
Worsening of ophthalmopathy
Possible radiation side effects
Surgical Thyroidectomy Adverse Effects
Permanent Hypothyroidism
Potential RLN Damage
Potential Hypoparathyroidism
Typical manifestations of Acromegaly
Coarsening of facial features
Pharyngeal Crowding
Hand/Feet Enlargement
What causes acromegaly?
Excessive growth hormone secretion
Often from a pituitary somatotroph adenoma
GH induces the liver to produce IGF-1, which causes excessive growth of bone & soft tissues
Cardiac manifestations of Acromegaly
Concentric Myocardial Hypertrophy
Diastolic Dysfunction
LV Dilation & Global Hypokinesis
Combined with concurrent HTN, OSA & valvular heart disease, can lead to heart failure & arrhythmias.
Anti-thyroid peroxidase autoantibodies
Painless (silent) thyroiditis
Does not require specific therapy, but beta blocker may be useful for symptomatic control
The effect of respiratory alkalosis on calcium homeostasis
Hydrogen ions dissociate from albumin
Calcium ions bind in their place
Ionized calcium is lower, though total body stores are constant
Symptoms of hypocalcemia manifest (paresthesias, hypercoagulability, etc)
Sequellae of Radioactive Iodine Therapy for Graves
Resolution of hyperthyroidism in 6 - 18 weeks
Permanent hypothyroidism in most patients
Worsening of Graves ophthalmopathy
Increased IL-6
Multiple Myeloma
Thyroiditis: Differentiating endogenous thyroid hormone release vs exogenous/factitious thyrotoxicosis
High Thyroglobulin - Endogenous release
Low Thyroglobulin - Exogenous use
Features of isolated premature adrenarche
Body Odor Oily Hair/Skin Acne Pubic Hair (pubarche) Axillary hair Elevated DHEAS, but low Testosterone
Euthyroid (Normal TSH) states that increase TBG
Estrogens (Pregnancy, OCPs, HRT)
Hepatic Dysfunction (acute hepatitis)
Medications (Tamoxifen)
Euthyroid (Normal TSH) states that decrease TBG
Hormonal abnormalities (Cushing's, glucocorticoids) Hypoproteinemia (Nephrotic Syndrome, Starvation) Medications (Niacin, high-dose androgens
Indications for BRCA Testing
FamHx Ovarian Cancer at any age
FamHx Breast Cancer <= 50 in first-degree relative
Typical presentation of Thyroid Lymphoma
Rapidly enlarging, firm goiter
Compressive symptoms (Dysphagia, Hoarseness)
Systemic B Symptoms (Fever, night sweats, weight loss)
Gland is frequently fixed, and doesn’t move up when swallowing.
More frequent in patients with Pre-existing Hashimoto’s
Pemberton Sign
When a thyroid lymphoma has retrosternal extension and compresses veins.
The sign is when the patient lifts their arms over their head and venous distension worsens due to compression of subclavians.
Positive TPO Antibodies
Hashimoto’s Thyroiditis
Treat with levothyroxine even if the patient is asymptomatic. It reduces titers of TPO antibodies, and reduces the risk of miscarriage
Primary treatment for papillary thyroid cancer
Surgical resection
After surgically removing papillary thyroid cancer? who gets adjuvant therapy?
Patients at increased risk of recurrence (large tumors, extrathyroidal invasion, lymph node metastasis, incomplete resection)
Radioiodine ablation & suppressive doses of thyroid hormone
Patient 3 - 4 months old Hypoglycemic (often with seizures) Lactic acidosis Hyperuricemia Hyperlipidemia
Doll-like face Rounded cheeks Thin extremities Short stature Protuberant abdomen
G6PD deficiency
Type 1 Glycogen Storage Disease
Von Gierke Disease
Glycogen builds up in organs and causes damage
Diarrhea (Smelly, Floating)
Weight Loss
Bone Pain
Steattorhea & Malabsorption
Chylomicron-mediated Vitamin D absorption is interrupted
Hypocalcemia & Hypophosphatemia
Secondary hyperparathyroidism leads to osteomalacia
What can cause Vitamin D deficiency?
Malabsorption
Intestinal bypass surgery
Celiac sprue
Chronic liver or kidney disease
What can cause Osteomalacia
Vitamin D deficiency (malabsorption, intestinal bypass surgery, celiac sprue, CKD or chronic liver disease)
Renal tubular acidosis (Proximal, Type 2)
Inadequate calcium intake
Paget’s disease of the bone
Accelerated focal bone remodeling:
Increased osteoclast activity
Rapid disorganized osteoblast activity
Normal serum calcium, phosphorous and PTH
Markers of bone resorption (c-telopeptide, n-telopeptide) and bone formation (alk phos, osteocalcin) are high
C-Telopeptide
N-Telopeptide
Markers of bone resorption
Osteocalcin
Alkaline Phosphatase
Markers of bone formation
Lytic bone lesions
Metastatic Breast Cancer
Renal Cell Carcinoma
Multiple Myeloma
Difference between thyrotoxicosis of painless (silent) thyroiditis & Grave’s disease on scintigraphy
Painless thyroiditis - Radioiodine uptake is decreased
Graves - Radioiodine uptake is increased
Positive Prussian Blue stain in urine
Hemosiderin is present
This indicates hemolysis
After getting an antibiotic for a UTI, a dude gets dark pee that stains prussian blue positive
G6PD. He’s hemolyzing after getting a sulfa drug
Hypothyroid patient becomes pregnant
Increase her levothyroxine dose
Increased thyroxine-binding globulin requires more thyroid hormone, but she can’t produce it on her own.
Increase by 30% at the time pregnancy is detected, then adjust every 4 weeks based on TSH
Risks of maternal hypothyroidism
Gestational hypertension
Preeclampsia
Premature delivery
Postpartum hemorrhage
Refeeding syndrome
Insulin increases for the first time in forever
Phosphorous, potassium & magnesium flood into the cells and out of the serum
Arrhythmias & cardiopulmonary failure result
Also seizures & wernicke encephalopathy
Hypopituitarism
Central Adrenal Insufficiency
Hypogonadotropic Hypogonadism
Central hypothyroidism
T4 is low
Cortisol is low
Aldosterone is normal (controlled by RAAS)
Most important initial step in managing Hyperosmolar Hyperglycemic State
Fluid resuscitation to save them from the osmotic diuresis.
Low calcium
High phosphate
High PTH
Secondary hyperparathyroidism
Caused by chronic renal failure retaining phosphate, which binds to circulating calcium.
That binding interferes with formation of 1,25 vitamin d
Less calcium is absorbed
Metformin: Things to know
First agent for most DMII patients
Weight neutral
Low risk of hypoglycemia
Lactic acidosis is a life-threatening complication
Sulfonylureas: Things to know
Generally added if metformin fails on its own
Weight gain & hypoglycemia are main side effects
Thiazoledinediones: Things to know
Used if unable to tolerate metformin or sulfonylureas
Side effects: Weight gain, edema, CHF, Bone fracture, bladder cancer
Low risk of hypoglycemia when used alone or with metformin
Can be used in renal insufficiency
DPP4 Inhibitors: Things to know
Low risk of hypoglycemia
Weight neutral
Can be used in renal insufficiency
GLP-1r Agonists: Things to know
Possible second agent if metformin fails alone
Especially good if weight loss is desired
Low hypoglycemia risk when used alone or with metformin
Associated with acute pancreatitis
When do you just observe a prolactinoma?
When it is asymptomatic and < 10mm
When do you use dopamine agonists (Cabergoline, Bromocriptine) to treat a prolactinoma?
When it is symptomatic and < 3cm
When do you resect a prolactinoma?
When it is symptomatic and >= 3cm
OR
When it increases in size while on dopamine agonist treatment
