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Zorluk: ZorEndocrinology and Metabolism

A 4646-year-old man presents to the clinic with an 88-month history of progressive fatigue, decreased libido, and generalized joint pain. He notes that the joint pain is most pronounced in the index and middle fingers of both hands. He also reports that his skin has become diffusely darker, despite working indoors year-round. He has no significant past medical history and takes no medications.

Physical examination reveals a firm liver edge palpable 33 cm below the right costal margin. Testes are small and soft bilaterally. There is bony enlargement and tenderness over the second and third metacarpophalangeal joints of both hands.

Laboratory results are as follows:
Fasting blood glucose: 138138 mg/dL
Sodium: 139139 mEq/L
Potassium: 4.14.1 mEq/L
Thyroid-stimulating hormone (TSH): 1.11.1 μ\mu U/mL (Normal: 0.5−5.00.5 - 5.0 μ\mu U/mL)
Free thyroxine (T4): 0.50.5 ng/dL (Normal: 0.9−1.70.9 - 1.7 ng/dL)
Total testosterone (8:008:00 AM): 140140 ng/dL (Normal: 300−1000300 - 1000 ng/dL)
Luteinizing hormone (LH): 1.21.2 mIU/mL (Normal: 1.5−9.31.5 - 9.3 mIU/mL)
Prolactin: 1212 ng/mL (Normal: 2−182 - 18 ng/mL)

Which of the following is the most appropriate next step in establishing the underlying etiology of this patient's condition?

  1. Measurement of transferrin saturation and serum ferritinCevap
  2. B
    Magnetic resonance imaging of the brain
  3. C
    Measurement of anti-thyroid peroxidase antibodies
  4. D
    Cosyntropin stimulation test
  5. E
    Measurement of serum insulin-like growth factor 1

Cevap

Measurement of transferrin saturation and serum ferritin
The correct answer is measurement of transferrin saturation and serum ferritin. This patient's clinical presentation is classic for hereditary hemochromatosis, a systemic disorder characterized by excessive iron absorption and deposition in parenchymal organs. The 'bronze diabetes' triad includes skin hyperpigmentation and diabetes mellitus. Iron deposition in the liver causes hepatomegaly, and deposition in the synovium leads to a characteristic arthropathy of the second and third metacarpophalangeal joints. Furthermore, iron deposition in the anterior pituitary gland preferentially disrupts gonadotropin and thyrotropin secretion, leading to secondary hypogonadism (low testosterone with normal or low LH) and secondary hypothyroidism (low free T4 with inappropriately normal TSH). The most appropriate initial screening test for hemochromatosis is the measurement of serum iron studies.

Adım Adım Çözüm

1
Interpret the patient's thyroid and gonadal laboratory results.
The patient has low free T4 and low testosterone with inappropriately normal TSH and LH levels.
To determine if the endocrine dysfunction is primary (end-organ failure) or secondary (central/pituitary failure).
2
Synthesize the central endocrine deficits with the systemic clinical findings.
The combination of secondary hypogonadism, secondary hypothyroidism, new-onset diabetes, hepatomegaly, hyperpigmentation, and specific second and third metacarpophalangeal arthropathy indicates an infiltrative systemic disease.
To identify the unifying underlying etiology.
3
Select the most appropriate initial diagnostic test for the suspected etiology.
Measurement of transferrin saturation and serum ferritin is the best initial step.
These are the standard screening tests for hereditary hemochromatosis before proceeding to confirmatory genetic testing.

Anahtar Kavram

Diagnosis of hereditary hemochromatosis presenting with anterior pituitary infiltration
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