Endocrine Disorders https://t.

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Normal TSH [0.4–4 mIU/L]
Normal TT4 [5–12 mcg/dL]
Normal FT4 [0.7–1.9 ng/dL]

I. Thyroid Disorders Normal TT3 [80–180 ng/dL]

Hypothyroidism (↓FT4) Hyperthyroidism (↑FT4)

Laboratory evaluation: DRUG-Induced: Laboratory evaluation: DRUG-Induced:
Typically treat the following: Amiodarone, Li ↑FT4, Low TSH (expt in TSH-secreting adenoma) Amiodarone, xxs
a. TSH > 5 mIU/mL with symptoms or with +ve Antithyroid antibodies Thyroid Hormones
Treatment
b. TSH= 10 mIU/mL without symptoms Hormotherapy
1. Radioactive iodine (131I)
Treatment: i. Most common treatment of HTR in the US
Levothyroxine, T4 (DOC): ii. Contraindication in pregnancy and in nursing mothers
iii. Very high risk of subsequent HoTR
Advantages over T3: less likelihood of cardiac S.E than T3 & no need for
2. Ablative Therapy DOC
multiple daily dosing.
 Often results in hypothyroidism.

“Liothyronine (synthetic T3), liotrix (synthetic T4/T3), desiccated thyroid 3. Thioamides:

are not recommended by leading professional organizations or clinical
guidelines”
 COUNSELLING POINTS
 Mean T4 replacement dosage of 1.6 mcg/kg/day typically
dosed in the morning on an empty stomach or at bedtime 4 hours after
last meal [COUNSEL]
 Different products may not be therapeutically equivalent. Choose one
product for the individual patient and remain with it.
 Monitoring:
 Titrate dose to normalization of TSH concentration; check TSH values
6–8 weeks after each dose or FT4 values 4-8 weeks after each dose.
 Use free T4 rather than TSH if central or secondary hypothyroidism
 Drug-Drug Interactions:
 Take T4 1–2 hours before or 4–6 hours after the following:
[Cholestyramine, Calcium, IRON, Antacids] ‫ ساعات‬4 ‫قبلهم بساعتين او بعدهم ب‬
 ADVERSE EFFECTS:
 Hyperthyroidism, Cardiac abnormalities &↑ Risk of fractures (usually
at higher dosages or over-supplementation)
 Special Populations:
 Pregnancy:
▶↑ Risk of miscarriage and ↓IQ of offspring
▶Treat even mildly elevated TSH values (Normal TSH: 0.4–3.0 mIU/L)
▶ Increase T4 replacement dose by 30% with first detection of
pregnancy [40%–50% T4 dose increase is required during pregnancy]
▶Monitor TSH concentration monthly and adjust dose accordingly.
 Infants: Dosage of 10–15 mcg/kg/day
▶Monitor with FT4 values for first 6 months and then TSH values
 Patients with preexisting cardiac disease: Start with low dose (12.5
mcg) and go slow (12.5-mcg increments every 6–8 weeks).
 Patients with preexisting osteopenia/osteoporosis (OP):
Be careful not to over-treat.
 Elderly: 50–60 years of age consider 50 mcg/day
Over-replacement results in potential of arrhythmias, angina, MI .
Maxedema Coma Subclinical hypothyrodism:
1-I.V T4 High TSH + normal T4
2-Antibiotics Who to treat?
3-hydrocortisone TSH 4.5-10 + Symptoms
Or Anti-thyroid antibodies
Or CVS disease , HF history or risk
1- Those awaiting ablative therapy or surgical resection; may use
Thioamides for 18–24 months in Graves' disease in an effort to achieve
disease remission
2- Those who are not ablative or surgical candidates (e.g: CVD)
Methimazole PTU (tid)
More Preferred unless first Preferred only during first
trimester of pregnancy, lactation, trimester of pregnancy
or thyroid storm (↓Embryopathy risk), lactation,
LESS HEPATOTOXICITY and thyroid storm
More Potent , SAME efficacy (Boxed warning Hepatotoxicity)
Baseline liver function tests (Routine evaluation not necessary)
Baseline CBC Testing (Routine evaluation not necessary)
Agranulocytosis usually occurs within first 3 months
Maximal effect may take 4–6 months
Counseling points:
▶A patient with HTR who is taking warfarin will need an increase in
warfarin dose as he or she becomes euthyroid while receiving thioamide
therapy.
▶The patient should report fever, sore throat, flu-like symptoms,
abdominal pain, dark urine, or lightly colored stool
4. Iodides: (Lugol solution, K Iodides)
a. Used for patients with Graves' disease 7-10 days before surgery to
shrink the gland [Do not use in the days before ablative iodine therapy]
↓uptake of radioactive iodine.
b. Can be used after ablative therapy (3–7 days) to inhibit thyroiditis-
mediated release of stored hormone
c. Used acutely in thyroid storm
Contraindication: Pregnancy, before undergoing RAI therapy.
5. β-Blockers: (propranolol Qid, nadolol) for symptomatic relief (e.g.,
palpitations, tachycardia, tremor, anxiety)
 Contraindications: Reactive airway disease (asthma, COPD).
 Alternatives: Clonidine, Non-DHP CCBs
Subclinical hyperthyroidism: (↑Risk of AF & Fractures)
Low TSH + Normal T4
Thyroid storm:
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PTU (or Methimazole), Iodine (1 hour after PTU), B-blockers,
Acetaminophen (Avoid NSAIDs), Corticosteroid (Prophylaxis
against relative adrenal insufficiency)
 II. Polycystic Ovary Syndrome
OGTT is recommended for all women with PCOS and BMI > 27 kg/m2
Treatment: Determine whether the patient seeks pregnancy and continue from there

1. Fertility improvement
A.E: Ovarian hyperstimulation syndrome, abdominal distention/bloating and multiple
Clomiphen pregnancies
C.I: Pregnancy, liver disease
Metformin
Aromatase inhibitor
therapy (letrozole,
anastrozole)
nd with or without clomiphene (Potential for hyperstimulation syndrome (swollen, painful
2 line recombinant FSH
ovaries)
Symptomatic improvement
1. Hyperandrogenism/hirsutism
st
A. Hormonal contraceptives: 1 line therapy for menstrual abnormalities, hirsutism, or acne ~non-androgenic progestin
(norgestimate, desogestrel, drospirenone)
B. Metformin:
Modest effect on hirsutism (Effective for metabolic and glycemic abnormalities)
Alternative to hormonal contraception for irregular menses when hormonal contraceptives are contraindicated
C. Spironolactone
-
D. Eflornithine Cream:
Decreased rate of hair growth ~ Do not wash skin for 8 hours after application
E. Flutamide
Hepatotoxicity concerns limit its use (check liver function tests [LFTs] monthly for first 4 months and then periodically.
Contraindicated in pregnancy
2. Insulin resistance
A. Metformin
B. Pioglitazone: Concerns about use during pregnancy, so not considered first line (Not Recommended)
3. Menstrual irregularities – Give Oral contraceptive
4. Endometrial hyperplasia – Give Oral contraceptive

III. Adrenal Gland Disorders

Hyposecretory cortisol (Addison disease )
Drug-induced: Ketoconazole, metyrapone,
aminoglutethimide, enzyme inducers
Treatment:
1-corticosteroids: Hydrocortisone, prednisone,
dexamethasone
2-mineralocorticoids: Fludrocortisone
3-DHEA  For women with decreased libido or low energy
Hypersecretory cortisol (Cushing syndrome )
1-Surgical resection ( ttt of choice )
2-Pasireotide: (dosage adjustments based on urinary free
cortisol and symptom improvements)  Monitor BG , LFT
& Gallbladder ultrasonography
3-Ketoconazole: A.E elevates liver enz. / gynecomastia
4-Mitotane: S.E: ataxia and Adrenocortical atrophy: Can
persist on discontinuation and, in severe cases, may
necessitate androgen and glucocorticoid replacement
5-Etomidate: IV( preferred when oral route is problematic)
6-Mifepristone: used in hyperglycemic patient.
7-Metyrapone: (by compassionate use only)
DOC for pregnant women. [SE.: HTN, Worsening of
hirsutism and acne if present before ttt]

Hyperaldosteronism
Hypernatremia, hypokalemia, hypomagnesemia, glucose intolerance. |Page2
Diagnosis: ↑Aldosterone/Renin Ratio
1-Spironolactone: hyperkalemia, gyncomastia
2-Eplerenone/ Amiloride
 IV. Pituitary Gland Disorders

Acromegaly (↑ GH ) GH deficiency
Diagnosis: 1-Recombinant GH
Failure of OGTT to suppress GH conc. +↑ IGF-1 (Somatropin)
GH alone are unreliable, given the pulsatile pattern of release in the body Administer in the evening.
Treatment: Linear growth of 5 cm/year
1-Surgery resection (TOC) expected. If growth rate does
2-Dopamine agonist ( Bromocriptine–Cabergoline)▶ Relative lack of efficacy not exceed 2.5 cm in 6
3-Somatostatin analogue ( Octreotide) : DOC months, double dose for next
Check values after 1 month of immediate release and after 3 months of depot inj. 6 months
A.E: GIT disturbances, hyperglycemia or hypoglycemia, Cholelithiasis, Hypothyroidism
 If response is adequate, can be changed to long-acting octreotide formulation Adults: non-weight based
adminis¬tered once monthly “UPDATE” dosing
Lanreotide SR (slow release) and lanreotide Autogel—Synthetic octapeptide
AE.:
Pasireotide: IM every 28 days 1. Arthralgias, injection-site
S.E: ↑LFTs (monitor 1–2 weeks after initiation then monthly x 3 months, then every 6 pain
months), Hyperglycemia, Cholelithiasis 2. Rare but serious cases of
idiopathic intracranial HTN.
4-GH receptor antagonist ( pegvisomant)
▶Reversible ↑LFTs (Monitor mthly for 6 mths)
Used in patients resistant to or intolerant of somatostatin analog therapy
Dosing is based on IGF-1 not GH values (overestimates true GH values).  EXAM
MRI every 6 months (because of concern about tumor growth)
Hyperprolactinemia
Clinical presentation
i. Amenorrhea, anovulation, infertility, hirsutism, and acne in women
ii. Erectile dysfunction, decreased libido, gynecomastia, and reduced muscle mass in men
iii. Headache, visual disturbances, bone loss
Drug induced (typically associated with prolactin<100 ng/ml(
Antipsychotics, TCAs, Metoclopramide, SSRI, Estrogen-progesterone, GnRH analogs, Methyldopa & Verapamil, opiates.

Bromocriptine Cabergoline
↑Nausea; preferred for fertility; recommended agent in Generally “preferred agent” due to better GIT tolerance
pregnancy
C.I: Patients with CAD, PAD and uncontrolled HTN
Consider tapering or discontinuing after 2 years of therapy if asymptomatic, prolactin concs normalized, and no tumor
remnant by imager.

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 V. Obesity
 No specific recommendations of a particular agent over another. Comparative studies between agents are lacking
(although liraglutide has been shown to reduce weight better than orlistat).
Obesity
Class I: BMI 30.0–34.9 kg/m2
Class II: BMI 35.0–39.9 kg/m2
Class III: BMI 40 kg/m2 or greater
Therapy Goal: Weight loss: Initial goal 5%–10% decrease from baseline weight over 6 months
Nonpharmacologic Therapy:
1. Increased physical activity: 200–300 minutes per week
2. Dietary options :
a. Strive for at least a 500-kcal/day deficit .
b. 1200–1800 kcal/day for women
c. 1500–1800 kcal/day for men
3. Surgery: Usually reserved for patients with severe obesity (BMI>40 kg/m2) or lower BMIs with existing comorbidities
a. Gastric bypass
b. Gastric banding
Bariatric surgery:
Pharmacotherapy:
BMI >30 Kg/m2 or BMI 27 kg/m2 + comorbidities [e.g., diabetes, hypertension])
Adverse effects Contraindications NOTES
Orlistat: ↓K, E, D, A vitamins, hepatotoxic, Chronic malabsorption syndrome Taken during or up to 1 hour after
kidney stones & Cholestasis meals
Lorcaserin (↑ serotonin) Avoid with SSRI MAOI use within 14 days Safety and efficacy have not been
Memory disturbances, Severe depression established in patients younger
hypoglycemia in DM pts Established cardiac valvular than 18 years.
disease
D.C if at least a 5% weight loss is
not achieved after 12 wks
Phentermine / XR topiramate " ↑B.P, HR, Insomnia, Depression / (a)MAOI use within 14 days Goal: > 5 % weight loss in 12 weeks
REMS" Substance abuse )b) Pregnancy (category X) / take at morning to avoid
)c) Glaucoma insomnia. (COUNSEL)
DOSING ‫ممي‬ )d) Hyperthyroidism
)e) Severe depression
)f) Recent stroke or CVD
(g) Nephrolithiasis.
Phentermine / XR topiramate " REMS"
If at least a 3% weight loss not achieved after 12 wks, can discontinue or increase to 11.25/ 69 mg daily for 2 weeks; then increase to 15/92 mg daily If
at least a 5% weight loss not achieved with 15/92 mg daily, discontinue use. Taper when discontinuing to avoid seizures.
Dosing in moderate hepatic or renal impairment: Do not exceed 7.5/46 mg daily.
 In women of childbearing age, obtain a negative pregnancy test before initiating and monthly thereafter because of fetal toxicity. Stress the
importance of adequate contraception during use.
Diethylpropion (schedule IV), ↑B.P, HR/ Substance abuse )a) MAOI use within 14 days) b) (approved for 12 weeks of
phentermine (schedule IV), Pulmonary HTN treatment); 3- to 4-kg weight loss)
phendimetrazine (schedule III) )c) Hyperthyroidism
)d) Coronary artery disease Avoid use beyond 12 wks.
(e) Glaucoma Avoid in patients with HTN or
(f) substance abuse HISTORY history of CVD
Bupropion HCl XR /Naltrexone HCl Boxed warning (bupropion) )a) Seizure disorder D.C use if at least a 5% weight loss
SUICIDAL THOUGHTS AND )b) Uncontrolled HTN is not achieved after 12 weeks of
BEHAVIORS; AND )c) Chronic opioid use use
NEUROPSYCHIATRIC REACTIONS )d) During or within 14 days of
taking MAOIs
)e) Pregnancy
(f) Known allergy
Liraglutide (SC) Target dosage higher in obesity
than in DM.
Avoid in pts receiving insulin due
to ↑ risk of hypoglycemia
 Avoid use with other GLP-1
agonists
Off-label medications used but not well studied specifically for obesity: SSRIs, zonisamide, metformin, pramlintide |Page4

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