Transcript Endocrinology I

Endocrine Board Review
LILLIAN F. LIEN, MD
DIVISION CHIEF
DIVISION OF ENDOCRINOLOGY, METABOLISM, & DIABETES
PROFESSOR OF MEDICINE, UMMC
Part I Diabetes
Lipids
Bone and Calcium
Thyroid
WITH APPRECIATION TO:
SARAH E. FRENCH, MD
Disclosures for
Dr. Lillian F. Lien
The Department of Medicine requests the following disclosures to the lecture audience:
Disclose relevant financial relationships with
any commercial interest:
Commercial Interest
Role
Medtuit
Co-owner
Springer
Book royalties
Sanofi-Aventis
Consultant
Merck
Consultant
Eli Lilly
Consultant
Novo Nordisk
Consultant
Endocrinology (8%)
17–19 questions
Diabetes mellitus
5–8
Thyroid disorders
2–4
Lipid disorders
2–3
Calcium metabolism and bone
1–5
Male reproductive health
1–2
Adrenal disorders
0–2
Hypertension
0–1
Female reproductive health
0–1
Hypothalamic disorders
0–1
Anterior pituitary disorders
0–1
Posterior pituitary/water metabolism
0–1
Endocrine tumors and endocrine
manifestations of tumors
0–1
Hypoglycemia not due to insulinoma
0–1
Polyglandular disorders
0–1
Nutritional disorders
0–1
Women’s health endocrine issues
0–1
Miscellaneous endocrine disorders
0–1
Diabetes

Predict the results of laser photocoag therapy for diabetic retinopathy

Treat Type 1, Diagnose Type 2

Differentiate Type 1 from Type 2 DM

Treat DKA

Diagnose cushing’s as a secondary cause of diabetes

Identify nocturnal hypoglycemia

Interpret A1c in pt with blood transfusion

Interpret A1c (vs post prandial excursions)

Treat diabetic neuropathy

Hypoglycemia workup

Hypoglycemia in the elderly / delayed / sulfonylurea

Diagnose post exercise hyperglycemia

Treat hypoglycemia unawareness

Counsel about the risks to infant of the mother’s gestational diabetes
Diabetes Definitions
FPG >126 mg/dl (7.0 mmol/l): Fasting is defined as no
caloric intake for at least 8 h.
Two-hr plasma glucose >200 mg/dl (11.1 mmol/l) during
an oral glucose tolerance test (OGTT): using a glucose
load containing the equivalent of 75 g glucose
In a patient with classic symptoms of hyperglycemia, a
random plasma glucose >200 mg/dL (11.1 mmol/l).
A1C >6.5%: The test should be performed in a
laboratory using a method that is National
Glycohemoglobin Standardization Program (NGSP)
certified and standardized to the DCCT assay.
DIABETES CARE, VOLUME 37 SUPPLEMENT 1, JANUARY 2014
Diabetes Mellitus

Type 1 Diabetes


Insulin deficiency
Type 2 Diabetes

Insulin resistance
Why Type 1 is very different from Type 2 Diabetes Mellitus!

Always give Basal Insulin (Lantus, Levemir, NPH) to your
Type 1 patient

Never Hold Basal insulin in Type 1, UNLESS BG is <80mg/dL


In that case, treat the patient. Once BG is above
80mg/dL, then be sure to give the Basal insulin at that
point, to avoid DKA later

Even if the patient is “NPO”, it is SAFE for all diabetic
patients, and NECESSARY for Type 1, to give the BASAL
insulin, for any BG over 80mg/dL
Pump patients with Type 1

As soon as pump is off, GIVE BASAL SQ INSULIN injection

If need help, call Endocrine Consults ASAP
Why Type 1 is very different from Type 2 Diabetes Mellitus!


Patients with Type 1 are Very Insulin Sensitive so need Small
Amounts!

Many patients with Type 1 have a total basal dose < 10 units

Correction for Type 1 should only be 1 to 4 units at the most –
whereas Correction for Type 2 can be much more.

Always ask “Does the pt have Type 1 or Type 2”
Patients with Type 1 can go into DKA at only Slightly Elevated
BGs

Even sugars of 200’s – 300’s can drive a Type 1 pt into DKA
Types of Diabetes Mellitus

Type 1 diabetes (5-10%)



Type 2 diabetes (90-95%)




Formerly “Type II”, “NIDDM”, “Adult Onset”
Gestational diabetes


Formerly “Type I”, “IDDM”, “Juvenile Onset”
Caused by destruction of insulin producing cells
Diabetes develops during pregnancy and
resolves after pregnancy
LADA –Latent Autoimmune Diabetes of
Adulthood
MODY –Maturity Onset Diabetes of the Young
Other causes (Cystic Fibrosis, MedicationInduced)
Genetics of Type 1 and LADA


Testing for Autoantibodies
may help establish DM1
diagnosis
GAD65, insulin(IAA), IA-2, Islet
cell (ICA), ZnT8

Autoantibody clustering is
different in LADA vs DM1

Clustering is characteristic in DM1;
pts often + for multiple
autoantibodies

Alternatively, LADA pts usually
positive for only one (usually
anti-GAD or ICA, possibly IA-2)
Secondary causes of
diabetes

Chronic pancreatitis

Cystic fibrosis

Hemochromatosis

Polycystic ovarian syndrome

Cushing’s syndrome

Acromegaly

Drugs: glucocorticoids, thyroid hormone,
thiazides, dilantin, alpha interferon

Somatostatinoma
A1c
 Goal
 Can
<7%
be unreliable if
Blood
transfusion
Decreased
RBC lifespan
Hemoglobinopathies

Metformin



Only oral agent that is
weight loss/weight
neutral

Generally first line
agent

Contraindicated if Cr
>1.5 in men, >1.4 in
females
Sulfonylurea

Insulin secretagogue

Contraindicated in
renal failure

TZDs

Can have fluid
retention and edema

Contrainidicated in
NYC Class III and IV
heart failure
DPP-4 inhibitors

Has direct effects on
insulin and glucagon

Delays gastric
emptying

Can be used in CKD
with dose reduction
Non-Insulin Anti-Diabetic
Medication
•Class
Approve
d Pre2005
Glipizide (Glucotrol),
Glimepiride (Amaryl ), Glyburide
(Diaßeta, Glynase PresTabs, Micronase)
Sulfonylurea

Metformin (Glucophage,
Glucophage XR)
Biguanide
Pioglitazone (Actos ),
Rosiglitazone (Avandia )
Thiazolidinedione
Repaglinide (Prandin),
Nateglinide (Starlix)
Meglitinide
Acarbose (Precose),
Miglitol (Glyset)
Alpha-glucosidase
inhibitor




Sitagliptin (Januvia),
Saxagliptin (Onglyza)
DPP-IV inhibitor
Exenatide (Byetta),
Liraglutide (Victoza)
GLP-1 mimetic
Pramlintide (Symlin)
Amylin mimetic
Bromocriptine mesylate
(Cycloset)
Dopamine receptor
agonist
Canagliflozin (Invokana)
SGLT2 inhibitor
Approved
Post-2005




DKA and HONK(HHNK…)

Acute,life-threatening consequences of uncontrolled
diabetes are hyperglycemia with
 Diabetic
Ketoacidoses = “DKA”

“THE WORSE I’VE EVER FELT”

Nausea, Vomiting

Weakness

Lethargy

Fruity Breath

Abdominal Pain

Hyperventilation
or the

Hyperosmolar nonketotic syndrome.
DKA: Management

Insulin drip

Fluid

Potassium

Insulin drip

EKG

Follow bicarb
and anion gap
Diabetes is not just
hyperglycemia




Acute complications

DKA

Hyperosmolar hyperglycemic
nonketotic state (HHNS)
Microvascular

Retinopathy

Neuropathy

Nephropathy

Follow Blood Pressure


Manage any
dyslipidemia


Macrovascular
ACE inhibitor or ARB if
proteinuria
Statins have the most
data
Screen for complications

Urine microalbumin,
dilated eye exam, feet

CAD

PVD

Smoking cessation

CVD

Immunizations
Atherosclerosis is most common
cause of death
Complications of Diabetes: Retinopathy

“uncontrolled neovascularization, termed proliferative diabetic
retinopathy (PDR), can result in severe and permanent vision loss.”
E, Neovascularization elsewhere (NVE) and two small vitreous hemorrhages (VH), also illustrating
high-risk proliferative diabetic retinopathy.
F, Extensive vitreous hemorrhage arising from severe neovascularization of the disc (NVD).

Panretinal laser photocoagulation therapy typically results in

Retained CENTRAL vision

But poorer peripheral and night vision
Diabetic Neuropathy

First Line Classes of Therapy

Voltage gated calcium channel ligand anticonvulsants


Serotonin norepi reuptake inhibitors



Pregabalin* and Gabapentin
Venlafaxine and Duloxetine*
Tricyclic Antidepressants – low dose

Amitriptyline

Desipramine
If on the maximally effective and or tolerated dosage of
one medication with no improvement, drug therapy should
be changed to a first line agent of a different class

*FDA approved for treatment of painful diabetic peripheral
neuropathy
Early morning
hyperglycemia


Dawn phenomenon

Rise in GH and cortisol lead to morning
hyperglycemia

No associated hypoglycemia
Somogy effect


Nocturnal hypoglycemia leads to morning
hyperglycemia
Only way to differentiate is to check 3 AM FSG
Hypoglycemia Hints

Treat hypoglycemia unawareness

Often by decreasing total daily insulin dose

Sulfonylureas (especially those with long half lives such as
glyburide) should not be used in the Elderly patient or with
impaired kidney function

In a patient with DM, Vigorous exercise should be
followed by consumption of Complex Carbohydrates –
especially if exercising in the evening (concern nocturnal
hypoglycemia)

IF NO evidence of nocturnal hypoglycemia, then can
suspect insufficient insulin as a cause of hyperglycemia …
3 am glucose
Adjusting insulin


Basal insulin—controls fasting glucoses

If fasting hyperglycemia—increase dose

If fasting hypoglycemia—decrease dose
Prandial insulin—controls post-prandial glucoses

If post-prandial hyperglycemia—increase dose

If post-prandial hypoglycemia—decrease dose
Definition of hypoglycemia


Whipple’s triad

Symptoms, signs or both consistent with hypoglycemia

A low plasma glucose concentration

Resolution of symptoms/signs after raising plasma glucose
“In the absence of Whipple’s triad, the
patient may be exposed to unnecessary
evaluation, costs and potential harms,
without expectation of benefit.”

From “Evaluation and Management of Adult Hypoglycemic
Disorders: An Endocrine Society Clinical Practice Guidelines”
Insulinoma

Extremely rare

Typically fasting hypoglycemia

Whipple’s triad

Have elevated insulin and C-peptide levels

Negative sulfonylurea screen
Interpreting laboratory data
Signs
Glucose
Insulin
Cpeptid
e
Proinsulin
β-hydroxybutyrate
Glucose
after
glucago
n
(+)
sulfonylurea
screen
Abs
Dx
No
< 55
<3
< 0.2
<5
> 2.7
< 25
No
-
Normal
Yes
< 55
>> 3
< 0.2
<5
≤ 2.7
> 25
No
-
Exogenous
insulin
Yes
< 55
≥3
≥ 0.2
≥5
≤ 2.7
> 25
No
-
Insulinoma
Gastric
bypass
Yes
< 55
≥3
≥ 0.2
≥5
≤ 2.7
> 25
Yes
-
Oral
hypoglycem
ic
Yes
< 55
>> 3
>>
0.2
>> 5
≤ 2.7
> 25
No
+
Insulin
Antibod
y
ADA Glycemic Goals for
Diabetes in pregnancy

For women with pre-existing type 1 or type 2
diabetes who become pregnant, a recent
consensus statement (106) recommended the
following as optimal glycemic goals, if they can be
achieved without excessive hypoglycemia:

premeal, bedtime, and overnight glucose
60–99 mg/dL (3.3–5.4 mmol/L)

peak postprandial glucose 100–129 mg/dL
(5.4–7.1 mmol/L)

A1C <6.0%

ADA Standards, DIABETES CARE, VOLUME 36, SUPPLEMENT 1,
JANUARY 2013
Levemir and Lantus

Lantus: Pregnancy category C: Use during pregnancy only if the potential
benefit justifies the potential risk to the fetus … There are no well-controlled
clinical studies of the use of LANTUS in pregnant women.

Levemir: Pregnancy Category B

“In an open-label clinical study, women with type 1 diabetes who were
(between weeks 8 and 12 of gestation) or intended to become pregnant
were randomized 1:1 to LEVEMIR® (once or twice daily) or NPH insulin
(once, twice or thrice daily). Insulin aspart was administered before each
meal. A total of 152 women in the LEVEMIR® arm and 158 women in the
NPH arm were or became pregnant during the study (total pregnant
women = 310).

In the 310 pregnant women, the mean glycosylated hemoglobin (HbA1c)
was < 7% at 10, 12, and 24 weeks of gestation in both arms. In the intent-totreat population, the adjusted mean HbA1c (standard error) at gestational
week 36 was 6.27% (0.053) in LEVEMIR®-treated patient (n=138) and 6.33%
(0.052) in NPH-treated patients (n=145); the difference was not clinically
significant.

No differences in pregnancy outcomes or the health of the fetus and
newborn were seen with LEVEMIR® use.”
Insulins in Pregnancy
Castorino K, Jovanovič L. Pregnancy and diabetes management: advances and controversies.
Clin Chem. 2011 Feb;57(2):221-30.
Diabetes in pregnancy

A1c < 7% before conception

Retinopathy may worsen during pregnancy

Remember: statins, ACEIs, and ARBs are
contraindicated
Gestational Diabetes

Infant has an increased risk of Childhood Obesity

50% of patients may go on to develop Type 2 over 10 years

NOT associated with MODY

NOT associated with Type 1
Lipids
Lipid profile

Ideally after 14 hour fast and no alcohol for 3 days

LDL is calculated


Total cholesterol – HDL – triglycerides/5

Not accurate if triglycerides > 400
VLDL and chylomicrons are rich in triglycerides
Hyperlipidemias

May be primary (genetic) or secondary (meds,
other diseases).

Hypercholesterolemia—elevated cholesterol with
normal triglycerides

Hypertriglyceridemia—elevated triglycerides with
normal cholesterol

Mixed hyperlipidemia—elevated cholesterol and
triglycerides
Familial hyperlipidemia


Lipoprotein lipase (LPL) deficiency “TYPE 1” (HIGH TRIG, nl chol)

Cannot degrade chylomicrons and VLDL

Triglycerides > 1000

Eruptive xanthomas with high triglycerides
Familial hypercholesterolemia “TYPE 2A” (nl trig, HIGH CHOL)

Reduction or absence of LDL receptor

Tendinous xanthomas
Familial hyperlipidemia


Familial combined hyperlipidemia
“Type 2B” (BOTH HIGH)

Most common genetic hyperlipidemia (1%)

Increase ApoB 100 → ↑LDL and ↑ VLDL

Premature CAD

No risk for xanthomas – just isolated xanthelasma
Familial dysbetalipoproteinemia
“Type 3” (BOTH HIGH)

Elevated IDL (total cholesterol and triglycerides)

Associated with diabetes, obesity and alcohol abuse

Palmar xanthomas (“yellow hands”)
Other classical
hyperlipidemias

Primary hypertriglyceridemia “TYPE 4” (HIGH TRIG, nl chol)


May or may not be associated with premature CAD
Mixed Hyperlipidemia
“TYPE 5” (BOTH HIGH)

High Cholesterol and High Triglycerides

Eruptive xanthoma

Only “may be associated” with premature CAD

Do not confuse with Type 2B Familial Combined
Tendon xanthoma
Elevated LDL
Familial hypercholesterolemia
Eruptive xanthomas
Elevated triglycerides
Tuberous xanthomas
Elevated triglycerides
Palmar xanthomas
Elevated IDL
Familial
dysbetalipoproteinemia
Normal retina
Lipemia retinalis
Elevated triglycerides
Lipid disorder scenarios
Young child with TG of 8000, pancreatitis, eruptive xanthomas,
lipemia retinalis, positive family history. Most likely diagnosis?
Lipoprotein lipase deficiency – unable to degrade VLDL and
chylomicrons.
32 yo man with CAD, LDL 350, TG normal and tendon xanthomas.
+Familly hx of premature CAD. Diagnosis?
Familial hypercholesterolemia (LDL receptor defect; LDL >300).
Autosomal dominant with variable penetrance.
48 yo woman with premature CAD and severe PVD. +Tuberous
and palmar xanthomata. TC 380, TG 400, LDL 50. Diagnosis?
Familial dysbetalipoproteinemia—High levels of IDL cause severe PVD and early
CAD. Treat with statins and fibrates. TC and TG roughly equal with low LDL.
Secondary hyperlipidemia

Increased LDL



Hypothyroidism
Increased triglycerides

Poorly controlled diabetes

Oral estrogens

Alcohol
Increased LDL and triglycerides

Nephrotic syndrome

HCTZ

Beta blockers

Glucocorticoids
Secondary hyperlipidemia

Treat secondary causes FIRST!

If hypothyroid, normalize TSH and then repeat lipid
profile.

If uncontrolled diabetes, normalize A1c and repeat
lipid profile.

If oral estrogens, change to patch or change
method of birth control.

If excessive alcohol intake, work on cessation
Treatment of
hyperlipidemia


LDL

Statins +/- ezetimibe

Bile acid resins
Triglycerides


Fibrates
Combined hyperlipidemia

Statin and fenofibrate (safer than gemfibrozil)

Niacin (best for HDL)
Lipid goals in diabetes


LDL

< 100 for every diabetic

< 70 high risk

First choice is statin – caution in female of child
bearing age
Triglycerides

<150

First treatment is glycemic control

Fenofibrate safer than gemfibrozil when in combo
with statin (less rhabdo)

Secondary target (treat LDL first) unless >500
BONE and calcium











Treat hypercalcemia
Diagnose FHH
Diagnose TB induced hypercalcemia
Diagnose humoral hypercalcemia of malignancy
Diagnose Paget’s disease
Diagnose Vitamin D deficiency
Manage post thyroidectomy hypoparathyroidism
Diagnose hungry bone
Manage hypocalcemia in alcoholism
Treat a female with low bone mass
Manage secondary osteoporosis
Hormonal regulation of
calcium
Parathyroid
hormone (PTH)

Increases serum calcium

Bone resorption

Renal resorption

Decreases phosphorus

Indirectly increases renal
hydroxylation of 25-OH
vitamin D to active form
of 1,25 (OH)2 vitamin D3
Vitamin D

Increases serum calcium


Intestinal absorption
Increases phosphorus
Clinical manifestations of
hypercalcemia


GI symptoms

Cardiac arrhythmias

Anorexia

Sinus bradycardia

Nausea

AV block

Vomiting

Shortening QT interval

Constipation
Nephrogenic diabetes
inspidius

Dehydration

Myopathy

Nephrolithiasis

Nephrocalcinosis

Band keratopathy

Pruritus

Altered mental status

Pancreatitis
Differential diagnosis of
hypercalcemia

Primary hyperparathyroidism

Malignancy

Granulomatous diseases

Thyrotoxicosis

Drugs

HCTZ

Lithium

Hypervitaminosis A

Hypervitaminosis D

Tertiary
hyperparathyroidism

Familial hypocalciuric
hypercalcemia

Immobilization

Milk-alkali syndrone
Primary
hyperparathyroidism

Most frequent cause of hypercalcemia as
outpatient

Often asymptomatic

Solitary adenoma (80%) >> four gland hyperplasia
(15-20%) >> carcinoma (< 1%)

Elevated or “inappropriately normal” PTH at the
same time as a high calcium consistent with
primary hyperparathyroidism (or FHH –non
surgical)
Secondary hyperparathyroidism

Treatment any underlying vitamin D deficiency

Vitamin D deficiency is secondary cause of
hyperparathyroidism

Watch renal function

Unlike primary and tertiary, will not have elevated
calcium
Tertiary hyperparathyroidism

Autonomous function; loss of negative feedback

Hypercalcemia
Indications for parathyroidectomy


Asymptomatic patients with

Age < 50

Severe hypercalcemia - usually >1
mg/dL above upper normal

Decreased glomerular filtration rate

Decreased bone density (revealing a T
score <-2.5) [3,4].
Symptomatic patients with

Polydipsia and polyuria

Nephrolithiasis

debilitating hyperparathyroid bone
disease - osteitis fibrosa cystica

bone pain and radiographically by

subperiosteal bone resorption on the
radial aspect of the middle phalanges

tapering of the distal clavicles

a "salt and pepper" appearance of the
skull

bone cysts, and brown tumors of the
long bones

Pancreatitis

Ulcer disease and GERD

Significant neurocognitive dysfunction
Recurrent Primary Hyperpara
 Familial syndromes – MEN,
Familial hyperparathyroidism
 Parathyroid cancer (rare)
 Parathyroid crisis



severe hypercalcemia with the
serum calcium concentration
usually above 14 mg/dL (3.8
mmol/L), and marked symptoms
of hypercalcemia, in particular,
central nervous system
dysfunction, nausea, and
vomiting.
In pts with ESRD

Refractory pruritus (see "Uremic
pruritus") in pt with ESRD

Progressive extraskeletal
calcification or calciphylaxis

Otherwise unexplained
myopathy (
Parathyroidectomy


Four-gland exploration

Mandatory in familial forms of hyperparathyroidism

Need experienced surgeon
Minimally invasive parathyroidectomy


Single gland involvement (adenoma)
Localization

Sestamibi scintigraphy

Neck ultrasound

Intra-operative measurements
Calcium scenarios
64 yo man with Calcium 10.8, PTH 135 (10-65). Diagnosis?
Primary Hyperparathyroidism
PTH is inappropriately normal - If >25 with hypercalcemia, then primary HPT
70 yo smoker with dysphagia to solids, then liquids; presents with
altered mental status and dehydration. Calcium 14, Albumin
2. Diagnosis?
Hypercalcemia of Malignancy
Malignancy-associated hypercalcemia

Altered mental status and dehydration

Tends to progress rapidly and have serum calcium >12 mg/dL

80% due to PTHrP –Humoral hyperca of malignancy



Hypercalcemia, hypophosphatemia, ↓PTH

Most commonly associated malignancies:

Squamous cell carcinoma of lung, esophagus, cervix, head/neck

Breast cancer

Lymphoma

Carcinoma of kidney, bladder and ovary
Local osteolytic hypercalcemia remaining 20%

Lytic metastasis with extensive destruction

Mediated by cytokines

Multiple myeloma and breast carcinoma
Rarely 1,25 (OH)2 vitamin D3 production

Hodgkin, B cell lymphoma, HTLV-1

Treatment: steroids
Familial hypocalciuric
hypercalcemia

Autosomal dominant mutation in calcium sensing
receptor

Usually asymptomatic

PTH inappropriately normal

Calcium clearance/creatinine clearance ratio
<0.01

Treatment: NO SURGERY
Granulomatous disease

Macrophages have 1-α-hydroxylase
which produces the active form 1,25
(OH)2 vitamin D3

Seen in sarcoidosis, tuberculosis,
histoplasmosis, leprosy, siliconeinduced granulomatosis

Treatment: steroids
Drug-induced
hypercalcemia

Thiazide


Lithium


Increased urinary calcium reabsorption
Resets calcium setpoint for PTH
Calcium carbonate (milk-alkali syndrome)

Generally >10 grams daily

Becoming more common (osteoporosis, ERSD)

62 yo woman evaluated for 1 week history of fatigue, lethargy,
constipation and nocturnal polyuria and polydipsia. Patient
has advanced breast cancer, which has metastasized to liver.
Conventional therapy is no longer helpful and she is
scheduled to see oncologist to discuss treatment.

Physical exam shows pale and somnolent woman. BP 98/65
and resting pulse 103. Mucous membranes dry. Liver edge
palpated 3 cm below costal margin.

Lab studies: BUN 37, calcium 15.7, creatinine 1.4, sodium 151.

What is most appropriate immediate next step in treating this
patient?

IV bisphosphonate

IV furosemide

IV glucocorticoids

IV normal saline
Treatment of
hypercalcemia

Hydration, hydration, hydration!

Bisphosphonates: pamidronate and zoledronic
acid

Effect is not immediate

Need to know Vitamin D status if pre-op patient (to
avoid post-op Hungry Bone Syndrome)

Steroids mainly for granulomatosis disease or
hematologic malignancies

Lasix is mainly for volume overload
Paget’s Disease

Disease of increased bone turnover
 Bone
pain with elevated alkaline phosphatase
 Bone
scan: focal uptake with no evidence of
cancer.


If affecting skull  osteoporosis circumscripta

Risk of cranial nerve palsies, particularly CN VIII

Risk of fracture at site of bone turnover
Therapy–bisphosphonate
Osteoporosis circumscripta
Hypocalcemia



Low vitamin D:
↓Ca ↓Phos ↑PTH

Secondary hyperparathyroidism is compensatory mechanism

Diagnosis of D deficiency – 25-OH-vitamin D level

Treatment: give vitamin D
Hypoparathyroidism:
↓ Ca ↑Phos ↓ PTH

Usually complication of total thyroidectomy

Treatment: calcium and calcitriol
Pseudohypoparathyroidism: ↓ Ca ↑Phos ↓ PTH

Defect in PTH receptor → PTH resistance

Characteristic phenotype: short, obese, round face, mental
retardation, short 4th and 5th metacarpals and metatarsals
Albright Hereditary Osteodystrophy
Hypocalcemia

Give IV calcium if symptomatic


Otherwise, give oral calcium and vitamin D



Calcium gluconate preferred to calcium chloride
Calcium chloride vs calcium citrate
Only treat to calcium of 8.0-8.5 (low normal)

Enough to prevent symptoms

Not enough to cause hypercalciuria
In a malnourished pt with alcoholism … suspect
both hypocalcemia and hypoMAGNESEMIA
Hungry bone syndrome

Usually occurs after parathyroidectomy

Hypocalcemia and Hypophosphatemia (even with normal PTH)

These are minerals consumed by the bone

The unmineralized bone matrix (produced during the period of hyperpara)
Begins To Mineralize after the PTH level becomes more normal

Potentially also HypoMagnesemia and HyperK

Requires an abrupt decrease in PTH release that upsets the equilibrium
between calcium efflux from bone and influx into the skeleton during bone
remodeling.

Risk Factors

Volume of the resected adenoma

Preoperative blood urea nitrogen concentration

Preoperative alkaline phosphatase concentration

Older age

Also – Vitamin D deficiency

MKSAP, UpToDate
Risk factors for
osteoporosis

Thin

Alcohol

Caucasian

Smoking

Female gender


First degree
relative with
osteoporosis
Rheumatoid
arthritis

Use of
glucocorticoids
Indications for bone
mineral density

Female > 65 years old

Post-menopausal female <65 years if:

1st degree relative, smoker, weight < 127 lbs

Male >70 years old

Fragility fracture

Glucocorticoids >3 months

Medical condition associated with osteoporosis

Hyperparathyroidism, Cushing’s disease, etc
Interpreting DEXA results

T-score compares patient to 30-year woman

Z-score compares patient to age-related controls

Normal—T-score > -1

Osteopenia—T-score > -1 but < -2.5


Use FRAX score to determine who to treat

If risk >3% hip and >20% any, treat patient
Osteoporosis—T-score < -2.5

Note causes of “Secondary osteoporosis /
osteopenia”

Malabsorption/celiac dz

Hypogonadism

Vitamin D deficiency

Primary Hyperparathyroidism

Multiple myeloma
Osteoporosis therapy
Drug
Spine
Hip
Bisphosphonates
+
+
Raloxifene
+
-
Tamoxifen
+
+
Calcitonin
+
-
Teriparatide
+
+
Useful for bone pain.
Tachyphylaxis limits use.
Stop use after 2 years →
risk of osteosarcoma.
Osteomalacia

Decreased bone mineralization usually from
vitamin D deficiency

In kids, we call it rickets

Typically older patient with bone pain and
proximal muscle weakness

Check 25-OH vitamin D and replace to >30
•

Also see ↓ Ca, ↓ PO4, ↑ alk phos, ↑ PTH
Work-up vitamin D deficiency
Calcium scenarios
68 yo woman with newly diagnosed osteoporosis
starts zoledronic acid therapy 2 days before
presentation and presents to the ER with tetany
and palpitations. What happened?
Bisphosphonate Induced Hypocalcemia - Most common
several days after infusion in Vitamin D deficient patients.
Always replace Vitamin D to 30 before starting
bisphosphonate therapy.
72 yo woman s/p parathyroidectomy due to primary
hyperparathyroidism develops calcium 6.9 on POD #1.
Magnesium is normal pre-op. Next step?
Check phosphorus level.
Low Phosphorus – Hungry Bone Syndrome – Give calcium/D
High Phosphorus – Hypoparathyroidism – Give Calcium/Rocaltrol
thyroid

Diagnose subacute thyroiditis

Treat Graves’ ophthalmopathy

Treat multinodular goiter

Thyroid storm

Treat hyperthyroidism in pregnancy

Evaluate thyroid nodules with FNA

Diagnose thyroid lymphoma

Manage medullary thyroid carcinoma

Treat Stage III thyroid ca with RAIManage subclinical
hypothyroidism

Manage hypothyroidism in pregnancy

Diagnose hypothyroidism in a critically ill patient

Treat myxedema coma

Diagnose a TSH stimulating pituitary tumor #28
Thyroid function tests (TFTs)

TSH

If ↓ TSH → hyperthyroidism OR SECONDARY HYPOthyroidism


In secondary hypothyroidism, replacement is adjusted with thyroid
hormone levels, not TSH

If ↑ TSH → Primary hypothyroidism

Use to screen and follow thyroid replacement
Total T4

All T4 (but 99.98% protein-bound)

↑TBG , ↑ total T4, normal free T4


Pregnancy, estrogens, tamoxifen, HIV, phenothiazines
↓ TBG , ↓ total T4, normal free T4

Androgens, glucocorticoids, nephrotic syndrome, cirrhosis
Thyroid function tests (TFTs)


Free T4

Key in diagnosis of central / secondary
hypothyroidism

Diagnosis and response to therapy in
hyperthyroidism
Total/free T3


Check if suspect T3 toxicosis
Thyroglobulin

Low in factitious thyrotoxicosis

Used to monitor thyroid cancer
Thyroid function tests (TFTs)


Thyroid uptake

Normal uptake approximately15%

↑uptake: Graves, toxic multinodular goiter, solitary
toxic adenoma

↓uptake: thyroiditis, factitious hyperthyroidism
Thyroid scan

Hot nodule = benign

Cold nodule > 1 cm needs FNA
Euthyroid sick syndrome

Seen in critically ill patients

Impairs body’s ability to peripherally convert T4 to T3


“Euthyroid sick”


T4 converts to reverse T3
See normal TSH, and abnormal free T3 and/or T4
“NON THYROIDAL ILLNESS SYNDROME “

Is the terminology when TSH is off – but still shouldn’t be more than
10 uu/mL

DON’T CHECK TFTs IN SICK PATIENTS unless you think it’s thyroid
storm or myxedema coma

Thyroid replacement would be controversial in euthyroid sick
Causes of hyperthyroidism
Graves disease (TSI/Trab,
Leakage or ExtraThyroidal Sources …
LO RAI UPTAKE
Toxic multinodular goiter
- Subacute Thyroiditis
Increased Production of
Thyroid Hormones
-
exophthalmos*)
-
(If goiter impinges on
trachea/esophagus/RLNerve,
consider thyroidectomy)
-
Molar Pregnancy (hCG)
-
Iodine-induced (JodBasedow)
-
TSH-pituitary adenoma
*Graves’ ophthalmopathy:
• Ophtho Referral!
• Steroids if severe
• Avoid radioactive iodine therapy
- Silent/post-partum
thyroiditis
- Thyrotoxicosis factitia
- Struma ovarii
Therapy for hyperthyroidism

Medical

Beta blocker (propranolol has T4 to T3 conversion
blocking)

Antithyroid Therapy – only works if hi-uptake

Propylthiouracil—pregnant patients (1st trimester),
thyroid storm



Monitor for hepatic failure, agranulocytosis, vasculitis
Methimazole—everybody else



Radioactive
iodine—delayed
effect

CAUTION IF
BAD Grave’s
orbitopathy

NOT in
pregnancy
Monitor for cholestasis, agranulocytosis, vasculitis
Steroids (stress-dose if concerned about thyroid
storm) – works if inflammatory/lo-uptake

Antithyroid therapies will not work in low uptake
states

Steroids also help with T4 to T3 conversion block
Unusual options more likely for thyroid storm:

SSKI – only 1 hour AFTER antithyroid therapy given

Lithium

Cholestyramine

Plasmapheresis

Surgery

requires preop
preparation
Amiodarone and the
thyroid


Amiodarone-induced thyrotoxicosis

Type 1: + underlying synthetic process

Type 2: destructive thyroiditis / inflammatory

Dx: Doppler ultrasound (vascular type 1; low flow in type 2)

Both have low RAI uptake but Type 1 has a tiny bit of uptake
whereas Type 2 has none
Amiodarone-induced hypothyroidism

Underlying + TPO antibodies

Give levothyroxine
Risk factors for thyroid
cancer

Family history

History of head/neck radiation

New nodule in patient <20 or >60 years old

Nodule that is firm, fixed and growing

Nodule with regional cervical LAD or Horner’s syndrome

Cold nodule on scan

Microcalcifications ± central bloodflow on US

Dysphagia, hoarseness, respiratory obstruction, pain
Evaluation of thyroid nodule

Obtain TSH.

If hyperthyroid, get thyroid
scan


If hot nodule, treat with
RAI ablation

Do NOT biopsy a hot
nodule!
If euthyroid or hypothyroid
and >1 cm, perform FNA

American Thyroid Association Guidelines
Smaller lesions with
concerning features may
be considered for biopsy
Cancer derived from
follicles

Anaplastic thyroid cancer


Extremely poor prognosis
Differentiated thyroid cancer (follicular epithelial cells)



Papillary thyroid cancer

Most common 85% of differentiated cancers

Grows slowly

Lymphangetic spread
Follicular thyroid cancer

10% of differentiated cancers

Hematogenous spread
Hurthle cell

3% of differented thyroid cancers

Oxyphil tumors
American Thyroid Association Guidelines

RECOMMENDATION 24
For patients with an isolated indeterminate solitary nodule who prefer a more
limited surgical procedure, thyroid lobectomy is recommended


Thyroid lobectomy alone may be sufficient treatment for small (<1 cm), low-risk
RECOMMENDATION 25
(a) Because of an increased risk for malignancy, total thyroidectomy is indicated in
patients with indeterminate nodules who have large tumors (>4 cm) …, in patients with
a family history of thyroid carcinoma, and in patients with a history of radiation
exposure.
(b) Patients with indeterminate nodules who have bilateral nodular disease, or those
who prefer… should also undergo total or near total thyroidectomy

RECOMMENDATION 26 -For patients with thyroid cancer >1 cm, the
initial surgical procedure should be a near-total or total thyroidectomy

Central neck dissection-often accompanies total thyroidectomy (may not

Post-op Radioactive Iodine (remnant) Ablation -for all patients with known
distant metastases, gross extrathyroidal extension of the tumor regardless
of tumor size, or primary tumor size >4 cm
do prophylactic dissection only if SMALL T1 or T2 non invasive PTC, follicular)
Medullary thyroid cancer

Most are sporadic (>80%) but can be familial (MEN
IIA/B, Familial nonMEN MTC)

Calcitonin levels helpful

Genetic tests available (RET oncogene)

Because MTC is often familial/MEN, always exclude
pheochromocytoma

Radioactive iodine is not taken up by C cells
(parafollicular cells) so NO RAI for MTC!

Nearly 30% -100% have bilateral disease – do total
thyroidectomy, NOT just lobectomy
Thyroid cases
Young patient with soft goiter, bruit, weight loss
Grave’s Disease  RAI ablation
Patient with sore throat, fever, painful goiter
Subacute thyroiditis
 Supportive care +/steroids
Thyroid cases
• Old pt. with weakness, weight loss, atrial fibrillation, goiter
– Apathetic hyperthyroidism (Toxic MNG)
• Young woman with molar pregnancy, hyperthyroid
– Very High hCG acts as TSH analog
• Health care worker with hyperthyroidism, no goiter, low RAIU
– Facticious (taking synthroid)  Check thyroblobulin (suppression)
Primary vs Secondary
Hypothyroidism


Primary hypothyroidism

Problem is the gland itself

Will see ↑TSH and ↓free T4
Secondary hypothyroidism

Problem is outside the gland (ie pituitary, etc)

Will see ↓ or ↔TSH and ↓free T4

Monitoring the TSH for treatment is not useful – follow
Free T4 instead
Question
An 84 yo lady with a history of dementia and no other medical
problems presents from the nursing home with altered mental
status. She is on no medications. She is unable to provide any
history but on your examination of her you find that she has a well
healed transverse scar across her neck. She is hypothermic,
bradycardic, has doughy skin and brittle hair. Labs are pending,
but you find a fingerstick glucose of 52.
Which of the following is the most reasonable next step in her care?
1.
Give her one amp of D50
2.
Levothyroxine 300mcg IV
3.
Levothyroxine 300mcg IV and hydrocortisone 100mg IV
4.
Levothyroxine 300mcg IV and one amp of D50 IV
5.
Levothyroxine 200mcg PO
Management of Myxedema Coma
Question
A psychiatrist in your community refers an 80 year old woman being
treated for depression. She reports generalized weakness, fatigue,
dry skin, weight gain and constipation. Her past medical history
includes CHF and stable angina. Your examination reveals periorbital edema, skin that is cool and dry, loss of the lateral third of
her eyebrow, mild bradycardia and a slow relaxation phase of her
deep tendon reflexes. You strongly suspect hypothyroidism and
check TSH and Free T4. The TSH is 95 units/mL and Free T4 is
0.1ng/dL (0.7-1.5ng/dL). She obviously has severe hypothyroidism.
Which of the following should you do next?
1.
Administer thyroxine 500mcg IV daily for 5 doses
2.
Administer thyroxine 500mcg IV and triiodothyronine 20mcg IV
daily for three days.
3.
Begin levothyroxine 300mcg PO daily
4.
Begin levothyroxine 100mcg PO daily
5.
Begin levothyroxine 25mcg PO daily
Replace levothyroxine slowly in elderly or cardiac patients
Hypothyroidism cases
27 year old woman with Hashimotos on
levothyroxine 88mcg daily, 2 weeks pregnant.
Estrogens increase TBG, so increase levothyroxine dose
by at least 30% during pregnancy
45 year old woman with Hashimotos has a rapidly
enlarging goiter
Thyroid Lymphoma - FNA diagnosis and irradiate
Subclinical Hypothyroidism

Defined as Elevated TSH but with all thyroid
hormone levels within the reference range

When do you treat these patients with
levothyroxine(synthroid)? (Not all of them):

TSH greater than 10 uu/mL

Presence of anti-thyroid peroxidase antibodies

Desire to become pregnant

High risk for progression to Overt Hypothyoiridms
with goiter or positive family history