A 38-year-old woman is evaluated in the outpatient clinic for a 6-month history of profoun… — USMLE Step 2 CK

A 38-year-old woman is evaluated in the outpatient clinic for a 6-month history of profound fatigue, progressive generalized weakness, dry skin, and constipation. She also reports frequent lightheadedness, particularly when standing up quickly. The patient has not menstruated for the past 5 months, although she previously had regular cycles. Her last pregnancy was 4 years ago and was uncomplicated. She takes no medications and does not use illicit drugs. Her body mass index is $22 \text{ kg/m}^2$ . Vital signs show a blood pressure of $92/58 \text{ mm Hg}$ while supine that drops to $80/50 \text{ mm Hg}$ upon standing. Her heart rate is $58/\text{min}$ . Physical examination reveals pale, dry skin and sparse axillary and pubic hair. The relaxation phase of the ankle reflexes is significantly delayed.

Laboratory studies show:
Hemoglobin: $11.2 \text{ g/dL}$
Sodium: $132 \text{ mEq/L}$
Potassium: $4.1 \text{ mEq/L}$
Thyroid-stimulating hormone (TSH): $0.15 \text{ \mu U/mL}$ (normal: $0.4 - 4.0 \text{ \mu U/mL}$ )
Free thyroxine (T4): $0.3 \text{ ng/dL}$ (normal: $0.9 - 2.4 \text{ ng/dL}$ )

Which of the following additional laboratory findings is most likely present in this patient?

Decreased serum morning cortisolAnswer
B
Elevated serum anti-thyroid peroxidase antibodies
C
Elevated serum adrenocorticotropic hormone
D
Decreased serum aldosterone concentration
E
Elevated serum follicle-stimulating hormone

Answer

Decreased serum morning cortisol

The correct answer is decreased serum morning cortisol because the patient's presentation and laboratory findings are highly consistent with panhypopituitarism. The presence of a low free T4 along with an inappropriately low TSH confirms secondary (central) hypothyroidism. The concurrent symptoms of orthostatic hypotension, hyponatremia, amenorrhea, and loss of axillary and pubic hair point to multiple anterior pituitary hormone deficiencies, specifically adrenocorticotropic hormone (ACTH) and gonadotropins. The reduction in ACTH leads to secondary adrenal insufficiency, which is biochemically characterized by a decreased serum morning cortisol level.

Step-by-Step Solution

Interpret the thyroid function tests.

The patient has a low free T4 (

0.3 \text{ ng/dL}

) with an inappropriately low TSH (

0.15 \text{ \mu U/mL}

), which points directly to secondary (central) hypothyroidism rather than a primary thyroid disorder.

In primary hypothyroidism, the low free T4 would trigger a loss of negative feedback, resulting in a markedly elevated TSH.

Correlate the central hypothyroidism with the rest of the clinical presentation.

The patient also has amenorrhea, orthostatic hypotension, mild hyponatremia, and loss of axillary/pubic hair, indicating involvement of the gonadal and adrenal axes.

Multiple hormone deficiencies (thyroid, gonadal, adrenal) of central origin confirm a diagnosis of panhypopituitarism.

Predict the expected laboratory values for the affected endocrine axes.

Because the anterior pituitary is failing, it cannot produce adequate adrenocorticotropic hormone (ACTH), leading to secondary adrenal insufficiency characterized by decreased serum morning cortisol.

Understanding the hypothalamic-pituitary-target organ axis allows one to anticipate that both the stimulating hormone (ACTH) and the target organ hormone (cortisol) will be low.

Key Concept

Patients presenting with secondary hypothyroidism (low free T4 and inappropriately low/normal TSH) frequently have concurrent deficiencies in other anterior pituitary hormones, known as panhypopituitarism, which typically manifests with secondary adrenal insufficiency (low cortisol, low/normal ACTH, normal aldosterone) and hypogonadotropic hypogonadism (low sex steroids, low/normal FSH/LH).

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