Endocrine Flashcards
subclinical hypothyroidism
clinical
- elevated TSH (verified on repeat measurements)
- normal free T4
- mild symptoms may or may no be present
indications for treatment
- TSH at least 10
- TSH 7-9.9
- age less than 70 - treat
- age 70 and up - treat if convincing hypothyroid symptoms
- TSH upper limit of normal - 6.9
- age less than 70 - treat if convincing hypothyroid symptoms, enlarging goiter, or elevated TPO anti-TPO titer
- 70 and up - do not treat (possible harm)
subclinical hypothyroid is defined as elevated TSH with normal free thyroxine. Most common cause is hashimoto (chronic lymphocytic) thyroiditis.
It’s associated with increased risk of pregnancy complications including recurrent miscarriage, severe preeclampsia, preterm birth, low birth weight, and placental abruption.
Anti-thyroid peroxidase antibodies (anti TPO) are associated with increased risk of pregnancy loss even in women who are euthyroid.
Glucagonoma
Rash - necrolytic migratory erythema. “rash started 3 weeks ago on forearm as a small elevated red area. gradually involved surrounding skin and became an erythematous itchy painful rash that did not respond to 1% hydrocortisone. 1 week ago the rash started clearing up from the center”
Rare pancreatic tumor associated with mild diabetes and a classic skin rash. Most are malignant and have mets, mainly in liver at the time of diagnosis. Some clinical manifestations are due to secretion of other peptides like VIP, calcitonin, and GLP1.
Diagnosis is suspected clinically and confirmed by measuring glucagon levels which are usually very high. Primary treatment is surgical
Postpartum thyroiditis
Primary hyperthyrodiism (elevated T4, suppressed TSH)
nontender goiter and recent pregnancy
Occurs less than a year following pregnancy
similar to silent thyroidism with thyroid peroxidase antibody. Transient hypothyroid phase before returning to a normal euthroyid state whereas patients with classic hashimoto have residual hypothyroidism
Radioactive iodine uptake scan can distinguish graves which causes increased thyroid hormone synthesis from postpartum thyroidism which are characterized by thryoid inflammation and release of preformed hormone. Graves has high RAIU.
postpartum pituitary necrosis
Sheehan syndrome. seen following severe OB hemorrhage and hypotension. Failure of lactation is a common presenting symptom but patients have central hypothyroidism rather than primary hyperthyroidism
type 1 vs 2 DM
Type 1
- insulin deficiency
- childhood or early adulthood, more common in whites
- usually rapid onset of clinical symptoms with osmotic symptoms
- DKA more common
- low C peptide levels
- pancreatic antibodies are usually present (glutamic acid decarboyxlase antibody)
Type 2
- insulin resistance with relative insulin deficiency
- adulthood, more common in nonwhites, more common in obese, positive family history
- asymptomatic at onset
- DKA less common
- C peptide usually elevated
- pancreatic antibodies usually absent
Diagnosis of hyperCa
1) Confirm hyperCa
- repeat testing
- correct for albumin or measure ionized calcium
2) next step is measur PTH
- high normal or high (PTH dependent)
- primary or tertiary hyperparathyroidism
- familial hypocalciuric hypercalcemia
- lithium
- suppressed PTH (PTH independent)
- measure PTHrP, 25-hydroxyD, 1,25-dihydroxyD
- malignancy’vit d def
- granulomatous dz
- drugs (thiazides)
- milk-alkali
- vit A roxicity
- thyrotoxicity
- immobilization
- measure PTHrP, 25-hydroxyD, 1,25-dihydroxyD
urinary calcium should be measured in patients iwht pTH dependent hyperCa to differentiate familial (rare dz due to mutations in calcium sensing receptor and leading ot low urinary ca excretion) from primary hyperpara (urinary ca is normal or high) but only after PTH-dependent hyperCa is confirmed
hyperCa of malignancy
Cause (3 causes)
1) PTHrP
- tumor type
- SCC
- renal and bladder
- breast and ovarian
- mechanism
- PTH mimic
- diagnosis
- low PTH
- high PTHrP
2) bone mets
- tumor type
- breast
- MM
- mechanism
- increased osteolysis
- diagnosis
- low PTH and PTHrP
- low Vitamin D
3) 1-25 dihydroxyD
- tumor type
- lymphoma
- mechanism
- increased calcium absorption
- diagnosis
- low PTH
- increased vitamin D
hyperCa of malignancy is associated with rapid onset of increased calcium levels.
Cushing’s Syndrome
HTN, hyperglycemia, osteoporosis, mood swings, hypoK, and metabolic alkalosis.
Screening for cushing’s can be done by overnight dexamethasone suppression test or 24h urinary free cortisol. In normal people, serum cortisol is typically suppressed below 3 mcg after giving 1 mg of dexamethasone. False positive results can be seen in alcoholism and malabsorption of dexamethasone
Screen young patients with diabetes, osteoporosis, HTN, and hypoK for cushings syndrome
Pioglitazone
Member of the thiazolidinedione class. It’s a PPAR-y agonist. PPAR-y receptors are in the collecting tubule of the nephron and stimulation by the drug leads to increased sodium reabsorption. This is the same channel via which aldosterone mediates effects on sodium retention
Fluid retention can occur in 4-6% of patients on thiazolidinediones, but most of these patients likely have underlying CHF
If these drugs cause fluid retention, treatment can be an aldosterone antagonist like spironolactone
Hyperthyroidism
Clinical features
- behavior disturbances (inattention, moodiness, poor school performance)
- weight loss
- goiter
- proptosis
- tachycardia, wide pulse pressure
- tremor, hyperreflexia
- warm, sweaty skin
diagnosis
- increased T3/T4, low TSH
- Thyroid stimulating immunoglobulin (Graves)
Tx
- methimazole
- plus/minus radioactive iodine
Complications
- arrhythmia, cardiomyopathy
- osteoporosis (elevated TH stimulates calcium and phosphate release from bone)
insulin dose and exercise
Physical activity promotes noninsulin-mediated uptake of glucose into skeletal muscles and increases risk of hypoglycemia in patients with diabetes. Risk is highest in type 1DM and type 2DM treated with insulin or insulin secretagogues (sulfonylureas)
Should decrease dose of short-acting insulin (lispro) within 1-3 hours prior to exercise, with reduction proportionate to exercise intensity. If prolonged (more than 60mins) or will occur in AM before breakfast, dosal of basal insulin (glargine) should also be reduced.
if glucose is less than 100 before, during or after exercise, additional carbs should be consumed.
Clinical features of thyrotoxicosis in older patients
CV
- AFib
- tachycardia (can be absent due to BBs or conduction defects)
- heart failure
Neuro
- apathy, confusion, depression
- tremor (often absent)
- proximal muscle weakness/wasting
endo
- proptosis, lid leg, thyromegaly
GI
- decreased appetite
- constipation
most common causes of AMS in elderly are meds, infections, and metabolic. dont forget thyroid. Thyroid stuff often presents atypically in an old person
Managing hyperglycemia in the hospital
1) Classify diabetes
- type 1 (do not stop basal insulin)
- type 2
- stress induced hyperglycemia
2) determine dietary status (eating normally, etc)
3) determine preadmission glycemic control and regimen
4) d/c oral drugs
5) determine insulin regimen
- basal-bolus
- patients with type 1
- patients with type 2 treated before admission with basal bolus regimen
- patients with type 2 not well controlled by ISS alone
- patients with newly diagnosed diabetes and high glucose levels
- ISS alone
- appropriate initially in pts whose type 2 is well controlled with diet and/or oral meds before admission. Adding basal insulin if glucose is suboptimally controlled on ISS alone
- insulin infusion (ICU)
- type 1 patients who are not eating and with glucose levels suboptimally controlled with subq insulin
- type 1 patients perioperatively or during labor
- hyperglycemic emergencies
in the hospital, goal is gluc in 140-180 range. Use 3 components
1) basal (intermediate or long acting) for controlling glucose levels btw meals. Needed for all type 1 patients and most type 2.
2) nutritional boluses (short acting) for controlling postprandial glucose excursions (not needed if pt not eating)
3) correctional boluses (short acting) for correcting high glucose levels (sliding scale)
basal (glargine, detemir, NPH)
short acting (aspart, lispro, glulisine)
generally, dose of prehosptal basal insulin should be lowered for admission bc they usually eat less in the hospital (25-50%)
Prolactinoma
clinical
- premenopausal women - oligo/amenorrhea, infertility, galactorrhea, hotflashes, decreased bone density
- post women - mass effect symptoms (HA, visual field defects)
- men - infertility, decreased libido, impotence, gynecomastia
labs/imaging
- serum prolactin often above 200
- rule out renal insufficiency (Cr) and hypothyroidism (TSH, thyroxine)
- MRI brain/pituitary
tx
- dopamine agonist (cabergoline, bromocriptine)
- trans-spneoidal surgery
High prolactin suppresses gonadotropin releasing hormone, LH, and estradiol leading to symptoms of hypogonadism like hot flashes, vaginal dryness, and osteoporosis***
Indications for diagnostic testing for pheo
Signs/symptoms
- episodic HAs, diaphoresis, tachycardia
- hyperadrenergic spells (nonexertional palpitations, pallor)
- resistant HTN or onset of HTN at young age
FHx
- pheo
- predisposing syndromes (MEN2, NF1, VHL)
Other
- adrenal incidentaloma on imaging
- pressor response during surgery/anesthesia
- idiopathic dilated cardiomyopathy
Measurement of 24h fractionated urinary metenephrines and catecholamine levels is one of the preferred screening tests. Also plasma free metanephrines. Prior to testing, stop TCAs, OTC decongestants) for 2 weeks.
24h urinary vanillylmandelic acid is much less sensitive
Beta block before alpha block may worsen HTN in pheo as unopposed alpha adrenergic activity may cause casoconstriction
Don’t start alpha blockers until after confirming diagnosis bc they can lead to a false positive (falsesly elevate catecholamines and metanephrines)
Steps for diagnosing a Pheo
High level of suspicion leads to 24h urine fractionated metanephrines/catecholamines or plasma fractionated metanephrines. If normal, recheck during a spell. If elevated (double/triple normal), next step is imaging (CT or MR abdomen)
If negative, consider further imaging
- MIBG scan
- octreotide scan
- whole body MR
- PET
If positive
- surgical eval
- genetic testing
- alpha and beta block prior to surgery
- MIBG scan if tumor more than 5cm and suspicion for extra-adrenal disease (younger patients and those with familial disorder)
removal is only performed after localization, adequate preop BP control for 10-14 days with an alpha blocker and intravascular fluid volume repletion with liberal fluid and salt.
intraop complications are much higher with inadequate preop alpha blockade and fluid deficiency. BBs are only given to patients with adequate and complete alpha blockade. Starting BB prior to AB leads to paradoxical increase in BP due to unopposed alpha adrenergic activity
surgical complications of adrenalectomy for pheo
Hypertensive crisis
- increased catecholamine release due to endotracheal intubation and adrenal gland manipulation
- increased serum norepinephrine with larger tumors (over 4cm)
- treat with iv nitroprusside, phentolamine or nicardipine
Hypotension
- reduced catecholamines after tumor removal
- persistent alpha blockade from preop long acting alpha blocker (phenoxybenzamine)
- treat with NS bolus, pressors if unresponsive
Hypoglycemia
- increased insulin secretion following tumor removal (catecholamines supress insulin secretion)
- treat with iv dextrose infusion
cardiac tachyarrhythmias
- increased catecholamine release from adrenal gland handling
- treat with iv lidocaine or esmolol
Treating Graves
Patients with symptomatic hyperthyroidism should be started on a beta blocker (propranolol) FIRST to reduce symptoms with additional measures to decrease thyroid hormone production and achieve euthyroid state. Options include antithyroid drugs, radioactive iodine, and thyroidectomy.
drugs inbibit synthesis of thyroid hormone. they can be used in short courses to achieve remission in mild cases and for chronic management in poor operative candidates or those who wish to avoid surgery/RAI. In patients with more severe symptoms, drugs can induce euthyroid state in preparation for surgery/RAI.
- methimazole is usually preferred due to risk of hepatotoxicity with propylthiouracil.
- PTU is recommended in 1st trimester of pregnancy tho bc methimazole is a teratogen
RAI is appropriate for patients who can’t tolerate drugs, those who wish to avoid surgery or peeps who will likely need more than drugs. Most patients treated with RAI for graves develop residual hypothyroidism and require long term thyroid replacement therapy.
- contraindicated in pregnancy and lactation
Surgery is preferred for those with large goiters, obstructive symptoms, or suspected thyroid cancer. Also recommended for significant ophthalmopathy as RAI may cause an exacerbation of symptoms in these patients.
Summary. BB to reduce symptoms (if symptomatic) followed by definitive treatment.
how do you monitor thyroid function during use of antithyroid drugs?
Use serum total T3/T4 as TSH may remain suppressed for several months following initiation of therapy and doesn’t reflect thyroid function status.
Get these labs 4-6 weeks after starting treatment. If normalized, can proceed to definitive therapy.
sulfonylurea overdose
Example is Glyburide. These drugs increase insulin secretion and can cause hypoglycemia.
First line treatment is dextrose. Look out for rebound hypoglycemia though.
Give octreotide which is a somatostatin analogue that lowers insulin secretion. Give when suspect large overdose or when patient doesnt know how much they took.
MEN1
Pituitary adenoma (10-20%)
- secretion of prolactin, growth hormone, ACTH
- mass effects (HA, visual fields)
Primary hyperparathyroidism (over 90%)
- multiple parathyroid adenomas or parathyroid hyperplasia
- hyperCa (polyuria, kidney stones, decreased bone density)
Pancreatic/GI neuroendocrine tumors (60-70%)
- GI - recurrent peptic ulcers
- gastrinoma/zollinger ellison
- insulinoma - hypoglycemia
- VIPoma - secretory diarrhea, hypoK, hypoCl
- glucagonoma - weight loss, necrolytic erythema, hyperglycemia
MEN2
2A
- medullary thyroid cancer (calcitonin)
- Pheo
- Primary hyperparathyroidism (parathyroid hyperplasia)
2B
- medullary thyroid cancer (calcitonin)
- Pheo
- mucosal neuromas/marfanoid habitus
Zollinger-Ellison
elevated serum gastrin
Gastrin can be high due to hyperCa or PPIs though. Don’t measure gastrin levels until patient has normal Ca level and has stopped PPI for 2 weeks
Congenital adrenal hyperplasia :(
CAH is a group of disorders characterized by deficiency in an enzyme involved in making steroids. Most cases are from auto recessive 21-hydroxylase deficiency. This causes low production of mineralocorticoids and glucocorticoids in addition to extra of its substrates. These extra substrates are then shunted towards androgen synthesis leading to ambiguous genitalia in girls and precocious puberty in boys. Adrenocorticotropic hormone levels are also high which causes hyperplasia of adrenal glands which leads to even more androgens.
- labs show low Na, high K, low glucose, high 17OH-progesterone
- treat with glucocorticoids and mineralocorticoids. High salt diet. genital reconstruction for girls. psychosocial support.
Salt wasting syndrome occurs in severe 21-hydrox deficiency and presents in first few weeks of life with life threatening emesis, dehydration and shock. Labs show low Na, high K (no aldosterone), high glucose (no cortisol)
1) 21-hydroxylase deficiency
- low mineralo
- low gluco
- high androgens
- salt wasting
- ambiguous genitalia in girls
2) 11B-hydroxylase deficiency
- high mineralo (low aldosterone but excessive weak mineralocoritcoid 11 deoxycorticosterone)
- low gluco
- high androgens
- HTN, lowK
- ambigious genitalia in girls
3) 17a-hydroxylase deficiency
- high mineralo
- high gluco (low cortisol but excessive weak glucocorticoid corticosterone)
- low androgens
- HTN, lowK
- ambigious genitalia in boys
- absent puberty
5 alpha reductase
converts testosterone to dihydrotestosterone
Elevated Testosterone to DHT ratio
autosomal recessive defect in XY males. Impaired verilization during embryo leading to abnormal/feminine external genitalia and normal internal genitalia.
Normal testosterone production. Normal estrogen levels. Normal or a little high LH.
Masculination during puberty when testosterone increases.
Management of DKA
IV fluids
- rapid infusion of NS
- add dextrose 5% when serum glucose is below 200
insulin
- IV infusion. Hold If K is less than 3.3
- switch to sq insulin (basal bolus) for the following
- able to eat
- glucose below 200
- anion gap below 12
- serum HCO3 at or above 15
- overlap sq and iv insulin by 1-2 hrs
K
- add iv K if serum K is less than 5.3. Hold if K reaches 5.3 or higher
- nearly all patients K is depleted, even with hyperK
HCO3
- consider for patients with pH of 6.9 or less
PO4
- consider if phosphate is less than 1, cardiac dysfunction, or respiratory depression
- monitor serum calcium
amiodarone and the thyroid
1) decreased conversion of T4 to T3.
- high t4
- low t3
- normal/high tsh
- no treatment needed
2) inhibition of thyroid hormone synthesis
- high tsh
- low t4
- give synthroid
3) amiodarone induced thyrotoxicosis type 1 (iodine induced increase in thyroid hormone synthesis)
- low tsh
- high t3 and t4
- low RAIU (radioactive iodine uptake)
- increased vascularity on ultrasound
- treat with antithyroid drugs
4) AIT type 2 (destructive)
- low tsh
- high t3 and t4
- undetectable RAIU
- decreased vascularity on US
- treat with steroids
menopausal hormone therapy
Most effective treatment for menopausal hot flashes. Improves vaginal atrophy, bone mass/fractures. Helps colon cancer, type 2 DM, and even has lower all cause mortality in patients under 60.
BUT
higher risk of DVT/PE, breast cancer, heart disease (especially in women over 60)
estrogen alone increases endometrial cancer (so combo is preferred)
Increased risk of stroke in all patients (small in younger patients but still increased) regardless of BP control or other risk factor mitigation.
MHT is safe for short period (3-5 years) in younger, low risk women (nonsmokers, no hx of breast cancer, clots, or CHD)
Maternal hypothyroidism in pregnancy
TSH
- low/suppressed in first trimester due to thyroid-stimulating actions of bhcg. Basically thyroid hormone increases during pregnancy and may cause a picture resembling subclinical hyperthyroidism
- pregnancy reference range for TSH
- first trimester: 0.1 - 2.5
- second 0.2 - 3
- third 0.3 - 3
Management
- increase levothyroxine dose by 30%
- monitor TSH levels every 4 weeks
- adjust dosage to maintain TSH within pregnancy reference ranges by trimester
Pernicious anemia
Look out! patients with autoimmune diseases (primary hypothyroidism) can get other ones!
Loss of intrinsic factor from parietal cells in stomach. Autoimmune destruction of parietal cells. Leads to b12 deficiency.
Neuro involvement of b12 deficiency leads to ataxia, loss of proprioceptive and vibratory sensations. Severe spasticity, weakness and peripheral nerve involvement too. Symptoms are usually worse in lower extremities.
when treating with b12 watch out for severe hypokalemia in first 48h. Closely monitor and supplement
SGLT2 inhibitors
Sodium-glucose cotransporter 2. Example is canaglifozin or dapaglifozin.
They lower blood glucose by reducing reabsorption of glucose in the kidney which leads to low insulin to glucagon ratio bc high blood glucose levels are the primary driver of insulin release.
Side effects
1) GU infections
- vulvovaginal candidiasis
- UTI
2) Fluid loss
- symptomatic hypotension
- AKI
3) Metabolic
- hyperK
- hyperlipidemia
- euglycemic DKA (gluc less than 250. manage with fluids, stopping drug, and control of glucose with insulin) - abdominal pain, metabolic acidosis, n/v, tachypnea
4) miscellaneous
- low trauma fractures
- amputation
hypoglycemia
blood glucose less than 60
whipple’s triad is strongly suggestive of true hypoglycemia. low glucose, symptoms of hypoglycemia, and improvement when given glucose.
familial hypocalciuric hypercalcemia vs primary hyperparathyroidism
FHH
- normal or mildly high serum Ca
- normal or high PTH
- no hypercalcemic symptoms
- normal bone density
- low urinary calcium excretion (Calcium to creatinine clearance ratio less tha 0.01 or 24h calcium less than 100mg)
- treatment is reassurance
PHPT
- high serum Ca
- normal or high PTH
- may have hyperCa symptoms
- often low bone density
- high CCCR (above 0.02) or 24h urinary calcium above 300 mg
- treat with parathyroidectomy or serial monitoring
Although PHPT causes increased reabsorption of calcium, net excretion is increased due to accelerated bone turnover. untreated PHPT can lead to CKD, renal stones and osteoporosis
short vs long insulin
short insulin has higher risk of hypoglcyemia than long acting.
Addison’s Disease
Chronic adrenal insufficiency
Weight loss, abdominal pain, fatigue, amenorrhea, asthenia, weakness, poor appetitie.
Muscle tenderness on exam, decreased axillary and pubic hair (low adrenal androgen production), increased pigmentation (co-secretion of ACTH and melanocyte stimulating hormone)
HypoNa, hyperK and mild hyperchloremic metabolic acidosis.
In evaluating the patient, measure morning plasma cortisol with concurrent ACTH. Low cortisol with high ACTH is diagnostic for primary adrenal insufficiency. If results are equivocal, they can be followed by ACTH stimulation test.
signs/symptoms of adrenal insufficiency
- get 250ug cosyntropin stimulation and ACTH/Cortisol levels
- indetermine
- further testing to assess pituitary function
- basal cortisol low, ACTH high, minimal cortisol response to cosyntropin
- primary adrenal insufficiency
- basal cortisol low, ACTH low, minimal or suboptimal cortisol response to cosyntropin
- secondary or tertiary adrenal insufficiency
- normal response (cortisol level above 20 30-60 mins after cosyntropin)
- unlikely to be adrenal insufficiency. Investigate other causes
- indetermine
delayed puberty in boys
Defined as lack of testicular enlargement by age 14
causes
- primary hypogonadism (elevated FSH and LH)
- klinefelter (47 xxy)
- secondary hypogonadism (due to impaired GnRH, low to normal FSH and LH)
- constitutional delay, chronic illness, malnutrition
- hypothyroidism, hyperprolactinemia
- kallmann syndrome
- craniopharyngioma
clinical
- absent testicular enlargement by age 14
- delayed growth spurt
initial workup
- FSH, LH, testosterone, TSH, prolactin
- bone age radiograph
