Pocket Medicine: The Massachusetts General Hospital Handbook of Internal Medicine (96 page)

HYPERTHYROIDISM

Etiologies
(
Lancet
2012;379:1155)
•
Graves’ disease
(60–80% of thyrotoxicosis) •
Thyroiditis
: thyrotoxic phase of subacute (granulomatous) or painless (lymphocytic) •
Toxic adenomas
(single or multinodular goiter) • TSH-secreting pituitary tumor or pituitary resistance to thyroid hormone (↑ TSH, ↑ free T
₄
) • Misc: amiodarone, iodine-induced, thyrotoxicosis factitia, struma ovarii (3% of ovarian dermoid tumors and teratomas), hCG-secreting tumors (eg, choriocarcinoma), large deposits of metastatic follicular thyroid cancer
Clinical manifestations of hyperthyroidism

• Restlessness, sweating, tremor, moist warm skin, fine hair, tachycardia, AF, weight loss, ↑ frequency of stools, menstrual irregularities, hyperreflexia, osteoporosis, stare and lid lag (due sympathetic overactivity) •
Apathetic thyrotoxicosis
: seen in elderly who can present with lethargy as only sx •
Thyroid storm
(extremely rare): delirium, fever, tachycardia, systolic hypertension but wide pulse pressure and ↓ MAP, GI symptoms; 20–50% mortality
Laboratory testing

•
↑ FT
₄
and
FT
₃
; ↓
TSH
(except in TSH-secreting tumors) •
RAIU scan
is very useful study to differentiate causes (see table on page 7-3); cannot do if recent IV contrast or amio load b/c iodine blocks uptake so ✓ autoantibodies instead • Rarely need to ✓ for autoantibodies except in pregnancy (to assess risk of fetal Graves’) • May see hypercalciuria ± hypercalcemia, ↑ AΦ, anemia
Graves’ disease
(
NEJM
2008;358:2594)
•
:
ratio is 5–10:1, most Pts between 40–60 y at dx •
thyroid antibodies
: TSI or TBII (
in 80%), anti-TPO, antithyroglobulin; ANA • Clinical manifestations in addition to those of hyperthyroidism (see above):

goiter
: diffuse, nontender, w/ thyroid bruit

ophthalmopathy
(
NEJM
2009;360:994): Seen in 50%; up to 90% if formally tested. Periorbital edema, lid retraction, proptosis, conjunctivitis, diplopia (EOM infiltration); associated w/ smoking. Stare and lid lag seen in any type of hyperthyroidism.

pretibial myxedema
(3%): infiltrative dermopathy

Thyroiditis
(
NEJM
2003;348:2646;
Med Clin North Am
2012;96:223)
•
Acute
: bacterial infection (very rare in U.S. except postsurgical) •
Subacute
: transient thyrotoxicosis → transient hypothyroidism → normal thyroid fxn

painful
(viral, granulomatous or de Quervain’s): fever, ↑ ESR; Rx = NSAIDs, ASA, steroids

silent
(postpartum, autoimmune including Hashimoto’s, or lymphocytic): painless,
TPO Abs; if postpartum, can recur with subsequent pregnancies

other
: amiodarone, palpation thyroiditis, after radiation

Treatment

• β-blockers: control tachycardia (propranolol also ↓ T
₄
→ T
₃
conversion) • Graves’ disease: either antithyroid drugs or radioactive iodine (
NEJM
2005;352:905)

methimazole
: 70% chance of recurrence after 1 y; side effects include pruritus, rash, arthralgia, fever, N/V and
agranulocytosis
in 0.5%. PTU: 2nd line (risk of hepatocellular necrosis; TID dosing; slower effect). For both, need to ✓ LFTs, WBC, TSH at baseline and in follow-up.

radioactive iodine (RAI)
(
NEJM
2011;364:542): typically done as outPt; preRx selected Pts w/ CV disease or elderly w/ antithyroid drugs to prevent ↑ thyrotoxicosis, stop 3 d before to allow RAI uptake; >75% of treated Pts become hypothyroid

surgery
: less commonly chosen for Graves’, usually for Pts w/ obstructive goiter or ophthalmopathy

• Toxic adenoma or toxic multinodular goiter: RAI or surgery (methimazole preRx for surgery, in selected patients before RAI) • Thyroid storm: β-blocker, PTU or methimazole, iopanoic acid or iodide (for Wolff-Chaikoff effect) >1 h after PTU, ± steroids (↓ T
₄
→ T
₃
) • Ophthalmopathy: can worsen after RAI, prevented by prophylactic Rx w/ prednisone in high-risk Pts; can be Rx’d w/ radiation and/or surgical decompression of orbits
Subclinical hyperthyroidism
(
Lancet
2012;379:1142)
• Mild ↓ TSH and
normal free T
₄
with only subtle or no sx • ~15% → overt hyperthyroidism in 2 y; ↑ risk of AF, CHD (
Archives
2012;172:799), osteoporosis • Rx controversial: consider if TSH <0.1 mU/L and ↑ risk for CV disease or osteopenic

NONTHYROIDAL ILLNESS (SICK EUTHYROID SYNDROME)

• TFT abnormalities in Pts w/ severe nonthyroidal illness (∴ in acute illness, ✓ TFTs only if ↑ concern for thyroid disease);
may
have acquired transient central hypothyroidism

• If thyroid dysfxn suspected in critically ill Pt, TSH alone not reliable; must measure total T
₄
, FT
₄
, & T
₃
(
J Endocrinol
2010;205:1)

• Mild illness: ↓ T
₄
→ T
₃
conversion, ↑ rT
₃
⇒ ↓ T
₃
; in severe illness: ↓ TBG & albumin, ↑↑ rT
₃
⇒ ↓↓ T
₃
, ↑ degradation of T
₄
, central ↓ TSH ⇒ ↓↓
T
₃
, ↓↓
T
₄
, ↓
FT
₄
, ↓
TSH

• Recovery phase: ↑ TSH followed by recovery of T
₄
and then T
₃

• Replacement thyroxine
not
helpful or recommended for critically ill Pts w/ ↓ T
₃
and T
₄
unless other s/s of hypothyroidism

AMIODARONE AND THYROID DISEASE

6 mg iodine per 200 mg tablet; risk of thyroid dysfunction lower with lower doses

✓
TSH prior to therapy, at 4-mo intervals on amio, and for
1
y after if amio d/c’d

Hypothyroidism
(occurs in ~10%; more common in iodine-replete areas)

• Pathophysiology

(1) Wolff-Chaikoff effect: iodine load ↓ I
^–
uptake, organification and release of T
₄
& T
₃

(2) inhibits T
₄
→ T
₃
conversion direct/immune-mediated thyroid destruction

• Normal individuals: ↓ T
₄
; then escape Wolff-Chaikoff effect and have ↑ T
₄
, ↓ T
₃
, ↑ TSH; then TSH normalizes (after 1–3 mo)

• Susceptible individuals (eg, subclinical Hashimoto’s, ∴ ✓ anti-TPO) do
not
escape effects

• Treatment: thyroxine to normalize TSH; may need larger than usual dose

Hyperthyroidism
(3% of Pts on amio; ∼10–20% of Pts
in iodine-deficient areas
)

• Type 1 = underlying multinodular goiter or autonomous thyroid tissue