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Fatigue: A patient is sick of being tired
This patient presented several challenges; we will therefore follow him in this issue and the next issue of Endocrine Today.
A 45-year-old man presents for an initial evaluation of progressive fatigue.
He was diagnosed with adrenal insufficiency three years ago after loss of consciousness and admission to the hospital for hyponatremia.
He has been treated with small doses of prednisone and has avoided further hospital admissions and hypotensive episodes. However, the patient started noticing erectile dysfunction as well as testicular shrinkage, hot flashes and loss of body hair about 10 months prior to his visit. He recalls that symptoms started after being treated with crotamiton cream for scabies one year ago. He had been started on testosterone gel 5 g daily (androgel 1%, Solvay) by a colleague one month prior to this visit, without significant effect on his fatigue. He states that his fatigue worsens when he increases his prednisone dose.
The patient describes decreased libido, erectile dysfunction and fatigue. He shaves twice per week and denies gynecomastia. His weight has been stable since an initial weight loss of 50 lb at the time of diagnosis with adrenal insufficiency.
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Other medical history: ulcerative colitis (quiescent), peptic ulcer disease, scabies, sinusitis and removal of anal fissure. Medications: mesalamine, prednisone and testosterone gel.
The patient has no known drug allergies, is married and is currently disabled due to his profound fatigue. He denies use of tobacco, alcohol or recreational drugs.
Physical exam is unremarkable, unless indicated otherwise below: blood pressure 110/70 mm Hg, pulse 65, height 6’, weight 183 lb. Phallus normal in shape and size, decreased urogenital hair distribution in female pattern distribution, testicles small at about 5 mL bilaterally
Rectal exam was deferred by the patient, who undergoes frequent examinations by his gastroenterologist and urologist. Morning labs off testosterone supplementation, with adjustment of steroid regimen: comprehensive metabolic profile normal, with a borderline sodium of 134 and potassium of 3.5, chloride 95 mmol/L. Prolactin low at 5. Total testosterone <2 ng/dL; luteinizing hormone 0.4; follicle-stimulating hormone 1.6 mIU/mL; sex hormone-binding globulin 43; cortisol 1.2; adrenocorticotropic hormone <5 pg/mL; dehydroepiandrosterone sulfate <15 meg/dL; thyroid-stimulating hormone 3.99 mIU/L; and erythrocyte sedimentation rate 12 mm per hour.
Reviewing the patient’s voluminous lab reports, there is a low insulin-like growth factor 1 level at 74 with a growth hormone <0.1. The patient recalls that an MRI of the pituitary was performed at the time of hospitalization three years ago and was read as normal.
What is the next best step to help this patient with profound fatigue?
A. Double the dose of testosterone gel to 10 g daily.
B. Order a repeat MRI of the pituitary and measure thyroid hormone levels in addition to TSH.
C. Start modafinil (Provigil, Cephalon) 100 mg daily.
D. Start a complete workup for rheumatologic comorbidities of ulcerative colitis.
E. Encourage the patient to press charges against the makers of crotamiton and the dermatologist who treated him for scabies.
CASE DISCUSSION:
Answer: B
Many middle-aged men come to see me for fatigue. They feel stressed by the demands placed on them in an increasingly tough work environment and their relationships. Many obese men also have hyperestrogenic hypogonadotropic hypogonadism, often associated with metabolic syndrome and sleep apnea. This patient, however, has adrenal insufficiency, one of the chief symptoms of which is fatigue. My initial instinct therefore was to increase the patient’s steroid dose, especially since he had ulcerative colitis. However, upon study of his extensive labs, I noticed that all of the axes of the anterior pituitary were low except for the TSH, without a corresponding free T4. In such a situation, one has to assume panhypopituitarism with an inappropriately normal TSH. This was indeed the case, as repeat thyroid function tests demonstrated a low free T4 at 0.5 ng/mL and a normal TSH at 2.7 mIU/L. Thyroid hormone supplementation was started, and growth hormone supplementation will be considered in the future. The patient has not yet had a repeat pituitary MRI (B) to help elucidate the etiology.
While many of the patient’s symptoms relate to sexual health and have not improved with testosterone supplementation, blindly increasing the dose without a monitoring level is not a good strategy (A). A repeat testosterone level on the current dose of supplementation was drawn. Modafinil does indeed help shift workers and narcoleptic patients stay awake, but it would not treat the underlying deficiency of thyroid hormone (C). A low ESR and worsening symptoms with increased glucocorticoid supplementation do not indicate a rheumatic comorbidity as the source of the patient’s fatigue. Finally, this patient was convinced that his hypogonadism was related to the treatment of scabies with a topical agent. While one should always be open for new side effects and report those for postmarketing safety, it is much more likely that the patient is having panhypopituitarism with gradual failure of all axes than initial hypoadrenalism and subsequent central hypogonadism as a previously unreported drug side effect (E). I was able to convince him that his scabies treatment was truly unrelated to his symptoms.
Ronald Tamler, MD, PhD, MBA, is Assistant Professor in the Division of Endocrinology at Mount Sinai School of Medicine, N.Y.