Acromegaly

A 50 year old male presents to the primary care physician with gradual onset of shortness of breath, headache, and visual disturbances over the past few months. He also reports fatigue, snoring at night, and daytime sleepiness. He has a history of hypertension and type 2 diabetes mellitus, for which he takes amlodipine and metformin. On examination, he has coarse facial features with a prominent forehead and prognathism, along with enlarged hands and feet. Blood pressure is 150/90 mm Hg. Laboratory evaluation shows elevated IGF-1. Oral glucose tolerance test demonstrates failure of growth hormone suppression. Echocardiography shows left ventricular hypertrophy with an ejection fraction of 55 percent. Pituitary MRI reveals a pituitary adenoma. Diagnosis?

Diagnosis is Acromegaly.

1. Definition

Acromegaly is a disorder caused by excess growth hormone secretion in adulthood, most commonly due to a somatotroph adenoma of the anterior pituitary, leading to elevated IGF-1 and progressive tissue overgrowth.

2. Etiology

2.1 Most Common Cause

1. Somatotroph pituitary adenoma

2.2 Other Causes

1. Ectopic growth hormone secretion
2. Excess growth hormone releasing hormone (GHRH)
3. Iatrogenic growth hormone excess

2.3 Familial Associations

1. MEN 1
2. Carney complex
3. McCune-Albright syndrome
4. Familial acromegaly

3. Pathophysiology

3.1 Core Mechanism

1. Excess growth hormone stimulates hepatic production of IGF-1
2. Increased IGF-1 causes soft tissue and bone overgrowth

3.2 Systemic Effects

1. Insulin resistance leading to type 2 diabetes mellitus
2. Cardiac remodeling causing biventricular hypertrophy and dysfunction
3. Soft tissue enlargement causing obstructive sleep apnea

4. Clinical Features

4.1 Somatic Features

1. Coarse facial features
2. Prominent forehead
3. Prognathism
4. Enlarged hands and feet
5. Widely spaced teeth

4.2 Soft Tissue and Skin Changes

1. Macroglossia
2. Thickened skin
3. Hyperhidrosis
4. Skin tags
5. Deepened voice

4.3 Neurologic and Mass Effect

1. Headache
2. Bitemporal hemianopia
3. Carpal tunnel syndrome

4.4 Metabolic and Systemic

1. Hypertension
2. Type 2 diabetes mellitus
3. Fatigue
4. Obstructive sleep apnea

4.5 Cardiovascular

1. Left ventricular hypertrophy
2. Diastolic dysfunction
3. Progression to heart failure
4. Arrhythmias and valvular disease

5. Diagnostic Evaluation

5.1 Screening

1. Elevated IGF-1

5.2 Confirmatory Test

1. Oral glucose tolerance test showing failure of GH suppression

5.3 Imaging

1. Pituitary MRI to identify adenoma

5.4 Additional Evaluation

1. Assessment of other pituitary hormones
2. Visual field testing
3. Screening for diabetes, dyslipidemia, and sleep apnea
4. Consider echocardiography
5. Consider colonoscopy based on guidelines

6. Complications

1. Cardiovascular disease
2. Respiratory complications including sleep apnea
3. Diabetes mellitus
4. Arthropathy
5. Carpal tunnel syndrome
6. Increased risk of colonic adenomas and colorectal cancer
7. Thyroid nodules

7. Management

7.1 First Line

1. Transsphenoidal surgery for pituitary adenoma

7.2 Medical Therapy

1. Somatostatin analogs such as octreotide, lanreotide, pasireotide
2. Dopamine agonists such as cabergoline or bromocriptine
3. Growth hormone receptor antagonist such as pegvisomant

7.3 Radiotherapy

1. For persistent or recurrent disease

7.4 Follow Up

1. Monitor GH and IGF-1 levels
2. Repeat pituitary imaging
3. Long term follow up due to risk of relapse

8. Key Clinical Insight

Coarse facial features + enlarged hands and feet + elevated IGF-1 + failure of GH suppression + pituitary adenoma = acromegaly

9. Exam Level Pearls

1. IGF-1 is the best screening test
2. OGTT confirms the diagnosis
3. Somatotroph adenoma is the most common cause
4. Transsphenoidal surgery is first line treatment
5. Mortality is mainly due to cardiovascular, respiratory, and neoplastic complications
6. Always look for sleep apnea, diabetes, and visual field defects

De Quervain thyroiditis

A 12 year old female presents to the endocrinology clinic with complaints of painful anterior neck swelling for 15 days. She also reports palpitations, sweating, and insomnia. There is a history of a recent upper respiratory infection 2 to 8 weeks prior to the onset of neck pain. On examination, blood pressure is 110/80 mm Hg, pulse rate is 102 beats per minute, respiratory rate is 18 breaths per minute, and temperature is 99.9 F. The thyroid gland is diffusely enlarged and tender on palpation. Thyroid function tests show low TSH with elevated T3 and T4 levels. Radioactive iodine uptake is decreased. Diagnosis?

Diagnosis is De Quervain thyroiditis (subacute granulomatous thyroiditis).

1. Definition

De Quervain thyroiditis is a self-limiting inflammatory disorder of the thyroid, most commonly triggered by a viral infection. It is associated with HLA B35 and is the most common cause of painful thyroiditis.

2. Etiology

2.1 Viral Trigger

1. Usually follows a viral upper respiratory infection
2. Occurs 2 to 8 weeks after infection
3. Often shows seasonal variation

3. Pathophysiology

3.1 Core Mechanism

1. Inflammatory destruction of thyroid follicular cells
2. Release of preformed T3 and T4
3. No new hormone synthesis

3.2 Disease Phases

1. Transient thyrotoxic phase
2. Euthyroid phase
3. Hypothyroid phase
4. Return to euthyroid state

4. Clinical Features

4.1 Core Features

1. Painful, tender thyroid
2. Neck pain radiating to jaw or ear
3. Low grade fever
4. History of recent viral illness

4.2 Thyrotoxic Symptoms

1. Palpitations
2. Sweating
3. Insomnia

4.3 Examination Findings

1. Diffuse thyroid tenderness

5. Diagnostic Evaluation

5.1 Thyroid Function Tests

1. Low TSH
2. Elevated T3 and T4

5.2 Inflammatory Markers

1. Elevated ESR
2. Elevated CRP

5.3 Radioactive Iodine Uptake

1. Low uptake

5.4 Ultrasound

1. Hypoechoic areas with reduced vascularity

5.5 Histopathology

1. Granulomatous inflammation with multinucleated giant cells

6. Key Diagnostic Insight

Painful thyroid + low RAIU + recent viral infection = De Quervain thyroiditis

7. Differential Diagnosis

1. Graves disease with increased RAIU
2. Hashimoto thyroiditis which is painless
3. Acute suppurative thyroiditis with systemic toxicity
4. Painless or postpartum thyroiditis

8. Management

8.1 General Course

1. Self-limiting condition, usually resolving within 3 to 4 months

8.2 Pain Control

1. NSAIDs or aspirin
2. Glucocorticoids for severe pain

8.3 Thyrotoxic Symptoms

1. Beta blockers such as propranolol
2. Antithyroid drugs are not indicated

8.4 Hypothyroid Phase

1. Levothyroxine only if symptomatic or TSH > 10

8.5 Monitoring

1. Thyroid function tests every 2 to 8 weeks

9. Complications

1. Transient hypothyroidism
2. Permanent hypothyroidism in a small percentage
3. Rare thyroid storm or arrhythmias

10. Key Clinical Insight

Hyperthyroidism due to hormone leakage, not increased synthesis, explains low RAIU

11. Exam Level Pearls

1. Painful thyroid is the key differentiator
2. Low RAIU distinguishes it from Graves disease
3. Triphasic course is classic
4. Post viral history is common
5. Antithyroid drugs should not be used

Coarctation of the Aorta

A 35 year old woman presents to the cardiology clinic with a five year history of hypertension requiring three antihypertensive medications. She reports persistent headaches, dizziness, and exertional dyspnea over several years. There is no family history of cardiovascular disease. On examination, blood pressure is 180/100 mm Hg in the right arm, while blood pressure in the lower extremities is reduced. Pulse rate is 88 per minute. Radial pulses are strong and brisk, whereas femoral pulses are weak and delayed, consistent with radiofemoral delay. Electrocardiography shows left ventricular hypertrophy. Chest X ray demonstrates bilateral rib notching and a focal indentation of the distal aortic arch consistent with the figure 3 sign. Echocardiography confirms LVH. Routine laboratory investigations and abdominal ultrasound are normal. Diagnosis?

Diagnosis is Coarctation of the Aorta.

1. Definition

Coarctation of the aorta is a congenital narrowing of the aorta, most commonly located just distal to the left subclavian artery near the ductus arteriosus in the juxtaductal region. It results in upper body hypertension and reduced lower body perfusion.

2. Etiology and Associations

2.1 Congenital

1. Juxtaductal narrowing of the aorta
2. May remain asymptomatic until adulthood

2.2 Common Associations

1. Bicuspid aortic valve
2. Turner syndrome
3. Berry aneurysms of the circle of Willis

3. Pathophysiology

3.1 Core Mechanism

1. Aortic narrowing increases afterload
2. Leads to left ventricular pressure overload
3. Causes left ventricular hypertrophy

3.2 Hemodynamic Effects

1. Proximal hypertension
2. Distal hypoperfusion
3. Activation of the renin angiotensin aldosterone system (RAAS) due to reduced renal perfusion

3.3 Collateral Circulation

1. Development of intercostal collateral vessels
2. Leads to rib notching

4. Clinical Features

4.1 Core Features

1. Resistant hypertension in a young patient
2. Headache and dizziness
3. Exertional dyspnea

4.2 Vascular Findings

1. Upper extremity BP > lower extremity BP
2. Radiofemoral delay
3. Weak femoral pulses

4.3 Additional Findings

1. Lower limb claudication
2. Systolic murmur best heard over the interscapular region

5. Diagnostic Evaluation

5.1 Chest X ray

1. Rib notching
2. Figure 3 sign

5.2 Electrocardiography

1. Left ventricular hypertrophy

5.3 Echocardiography

1. Assesses LVH
2. May have limited visualization of coarctation in adults, but is useful for identifying associated cardiac abnormalities

5.4 CT Angiography or Cardiac MRI

1. Preferred imaging modality in adults
2. Defines location, severity, and collateral circulation

6. Hemodynamic Profile

1. Upper limb hypertension
2. Lower limb hypotension
3. Pressure gradient > 20 mm Hg

7. Complications

1. Aortic dissection or rupture
2. Intracranial hemorrhage due to berry aneurysm
3. Heart failure
4. Premature coronary artery disease
5. Persistent hypertension after repair

8. Management

8.1 Indications

1. Pressure gradient > 20 mm Hg
2. Hypertension
3. Left ventricular hypertrophy

8.2 Definitive Treatment

1. Endovascular stent placement preferred in adults
2. Surgical repair with resection and anastomosis

8.3 Long Term Care

1. Lifelong follow up
2. Monitor for persistent hypertension
3. Risk of recoarctation and aneurysm formation

9. Key Clinical Insight

Resistant hypertension + radiofemoral delay + rib notching = coarctation of the aorta

10. Exam Level Pearls

1. Upper limb hypertension with lower limb hypotension is classic
2. Rib notching indicates collateral circulation
3. Bicuspid aortic valve is a common association
4. CT angiography is preferred in adults
5. Hypertension may persist even after repair